PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
2862087-2	1985	Reduction in HbA1c with basal insulin supplement, sulfonylurea, or biguanide therapy in maturity-onset diabetes.	Biguanides	67-76	hemoglobin subunit alpha 1	Homo sapiens	13-17
2656043-2	1989	Oral hypoglycaemic drugs, sulphonylureas and biguanides, occupy an important place in the treatment of Type II (non-insulin-dependent) diabetic patients who fail to respond satisfactorily to diet therapy and physical exercise.	Biguanides	45-55	insulin	Homo sapiens	116-123
3552509-2	1987	The mechanism of action of metformin and other biguanides is not completely understood, but recent in vitro and in vivo studies suggest that metformin may act in part by both increasing the binding of insulin to its receptor and potentiating insulin action.	Biguanides	47-57	insulin	Homo sapiens	201-208
4046836-1	1985	The biguanides have been shown to reduce insulin requirements in type I (insulin-dependent) diabetic patients with an increase in insulin binding to insulin receptors.	Biguanides	4-14	insulin	Homo sapiens	41-48
4046836-1	1985	The biguanides have been shown to reduce insulin requirements in type I (insulin-dependent) diabetic patients with an increase in insulin binding to insulin receptors.	Biguanides	4-14	insulin	Homo sapiens	73-80
4046836-1	1985	The biguanides have been shown to reduce insulin requirements in type I (insulin-dependent) diabetic patients with an increase in insulin binding to insulin receptors.	Biguanides	4-14	insulin	Homo sapiens	73-80
4046836-1	1985	The biguanides have been shown to reduce insulin requirements in type I (insulin-dependent) diabetic patients with an increase in insulin binding to insulin receptors.	Biguanides	4-14	insulin	Homo sapiens	73-80
2701482-9	1989	Further indication of structural alteration of biguanide-treated mucin was given by its loss of solubility in 0.22 M-sodium thiocyanate.	Biguanides	47-56	LOC100508689	Homo sapiens	65-70
3908277-1	1985	Although biguanides are widely used in the treatment of non-insulin- dependent diabetic patients, the underlying mechanism for their antidiabetic effects is not fully understood.	Biguanides	9-19	insulin	Homo sapiens	60-67
6734405-0	1984	Effects of biguanides and sulfonylureas on insulin receptors in cultured cells.	Biguanides	11-21	insulin	Homo sapiens	43-50
6734405-3	1984	In contrast the two biguanides tested, phenformin and metformin, increased insulin binding in all cell types by 44 to 101%.	Biguanides	20-30	insulin	Homo sapiens	75-82
6734405-4	1984	These studies raise the possibility, therefore, that biguanides may have a direct effect on insulin receptors and this effect may account for the known effects of biguanides to lower elevated blood sugar levels in diabetic patients.	Biguanides	53-63	insulin	Homo sapiens	92-99
6734405-4	1984	These studies raise the possibility, therefore, that biguanides may have a direct effect on insulin receptors and this effect may account for the known effects of biguanides to lower elevated blood sugar levels in diabetic patients.	Biguanides	163-173	insulin	Homo sapiens	92-99
6350337-1	1983	In order to evaluate the in vivo effects of biguanides on the insulin receptor, we have studied insulin binding to circulating monocytes of six normal controls, eight obese nondiabetic subjects, and six obese type II diabetic patients, both before and after 4 days of treatment with the biguanide metformin (850 mg twice daily orally).	Biguanides	44-54	insulin	Homo sapiens	62-69
6376023-1	1984	We evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo.	Biguanides	50-59	insulin	Homo sapiens	117-124
6350337-1	1983	In order to evaluate the in vivo effects of biguanides on the insulin receptor, we have studied insulin binding to circulating monocytes of six normal controls, eight obese nondiabetic subjects, and six obese type II diabetic patients, both before and after 4 days of treatment with the biguanide metformin (850 mg twice daily orally).	Biguanides	44-53	insulin	Homo sapiens	62-69
6345751-3	1983	The antidiabetic action of phenformin and other related biguanides can be explained in terms of competition between these molecules and insulin to coordinate cationic oligoelements together with their ability to form hydrogen bonds between the biguanide moiety and insulin itself.	Biguanides	56-66	insulin	Homo sapiens	136-143
6345751-3	1983	The antidiabetic action of phenformin and other related biguanides can be explained in terms of competition between these molecules and insulin to coordinate cationic oligoelements together with their ability to form hydrogen bonds between the biguanide moiety and insulin itself.	Biguanides	56-66	insulin	Homo sapiens	265-272
6345751-3	1983	The antidiabetic action of phenformin and other related biguanides can be explained in terms of competition between these molecules and insulin to coordinate cationic oligoelements together with their ability to form hydrogen bonds between the biguanide moiety and insulin itself.	Biguanides	56-65	insulin	Homo sapiens	136-143
6345751-3	1983	The antidiabetic action of phenformin and other related biguanides can be explained in terms of competition between these molecules and insulin to coordinate cationic oligoelements together with their ability to form hydrogen bonds between the biguanide moiety and insulin itself.	Biguanides	56-65	insulin	Homo sapiens	265-272
6749582-1	1982	It has been suggested that biguanides should be used in Type 1 (insulin-dependent) diabetic patients in order to diminish insulin requirements and reduce the chances of insulin reactions.	Biguanides	27-37	insulin	Homo sapiens	64-71
6754220-0	1982	[A case of lactic acidosis, induced by biguanides, treated with insulin and glucose].	Biguanides	39-49	insulin	Homo sapiens	64-71
6751898-1	1982	The effect of the biguanide metformin (dimethyl-biguanide) on insulin binding in vitro to IM-9 lymphocytes and MCF-7 human breast cancer cells was studied.	Biguanides	18-27	insulin	Homo sapiens	62-69
7033271-9	1982	Therefore, these studies suggest that: 1) in vitro, biguanides enhance insulin binding to its receptors in a variety of cell types; 2) this effect of biguanides doesn"t depend on new receptor synthesis; it is a result of changes in the affinity of the insulin receptor; and 3) in contrast to the biguanides, the sulfonylureas do not have a major direct effect on insulin binding to its receptors in most cell types.	Biguanides	52-62	insulin	Homo sapiens	71-78
7033271-9	1982	Therefore, these studies suggest that: 1) in vitro, biguanides enhance insulin binding to its receptors in a variety of cell types; 2) this effect of biguanides doesn"t depend on new receptor synthesis; it is a result of changes in the affinity of the insulin receptor; and 3) in contrast to the biguanides, the sulfonylureas do not have a major direct effect on insulin binding to its receptors in most cell types.	Biguanides	52-62	insulin receptor	Homo sapiens	252-275
7033271-0	1982	Comparison of the in vitro effect of biguanides and sulfonylureas on insulin binding of its receptors in target cells.	Biguanides	37-47	insulin	Homo sapiens	69-76
7033271-9	1982	Therefore, these studies suggest that: 1) in vitro, biguanides enhance insulin binding to its receptors in a variety of cell types; 2) this effect of biguanides doesn"t depend on new receptor synthesis; it is a result of changes in the affinity of the insulin receptor; and 3) in contrast to the biguanides, the sulfonylureas do not have a major direct effect on insulin binding to its receptors in most cell types.	Biguanides	52-62	insulin	Homo sapiens	252-259
7033271-9	1982	Therefore, these studies suggest that: 1) in vitro, biguanides enhance insulin binding to its receptors in a variety of cell types; 2) this effect of biguanides doesn"t depend on new receptor synthesis; it is a result of changes in the affinity of the insulin receptor; and 3) in contrast to the biguanides, the sulfonylureas do not have a major direct effect on insulin binding to its receptors in most cell types.	Biguanides	150-160	insulin	Homo sapiens	71-78
7033271-9	1982	Therefore, these studies suggest that: 1) in vitro, biguanides enhance insulin binding to its receptors in a variety of cell types; 2) this effect of biguanides doesn"t depend on new receptor synthesis; it is a result of changes in the affinity of the insulin receptor; and 3) in contrast to the biguanides, the sulfonylureas do not have a major direct effect on insulin binding to its receptors in most cell types.	Biguanides	150-160	insulin receptor	Homo sapiens	252-275
7033271-9	1982	Therefore, these studies suggest that: 1) in vitro, biguanides enhance insulin binding to its receptors in a variety of cell types; 2) this effect of biguanides doesn"t depend on new receptor synthesis; it is a result of changes in the affinity of the insulin receptor; and 3) in contrast to the biguanides, the sulfonylureas do not have a major direct effect on insulin binding to its receptors in most cell types.	Biguanides	150-160	insulin	Homo sapiens	252-259
7033271-9	1982	Therefore, these studies suggest that: 1) in vitro, biguanides enhance insulin binding to its receptors in a variety of cell types; 2) this effect of biguanides doesn"t depend on new receptor synthesis; it is a result of changes in the affinity of the insulin receptor; and 3) in contrast to the biguanides, the sulfonylureas do not have a major direct effect on insulin binding to its receptors in most cell types.	Biguanides	150-160	insulin	Homo sapiens	71-78
7033271-9	1982	Therefore, these studies suggest that: 1) in vitro, biguanides enhance insulin binding to its receptors in a variety of cell types; 2) this effect of biguanides doesn"t depend on new receptor synthesis; it is a result of changes in the affinity of the insulin receptor; and 3) in contrast to the biguanides, the sulfonylureas do not have a major direct effect on insulin binding to its receptors in most cell types.	Biguanides	150-160	insulin receptor	Homo sapiens	252-275
7033271-9	1982	Therefore, these studies suggest that: 1) in vitro, biguanides enhance insulin binding to its receptors in a variety of cell types; 2) this effect of biguanides doesn"t depend on new receptor synthesis; it is a result of changes in the affinity of the insulin receptor; and 3) in contrast to the biguanides, the sulfonylureas do not have a major direct effect on insulin binding to its receptors in most cell types.	Biguanides	150-160	insulin	Homo sapiens	252-259
654296-3	1978	All 3 biguanide preparations induce hyperlactaemia in diabetics.	Biguanides	6-15	paired box 5	Homo sapiens	0-5
7019705-0	1981	Biguanide treatment increases the number of insulin-receptor sites on human erythrocytes.	Biguanides	0-9	insulin receptor	Homo sapiens	44-60
7391178-3	1980	The biguanides can be detected in serum at concentrations in the region of 60 ng ml-1 and preliminary results are presented to show the variation of proguanil in serum over a 24-h peroid following ingestion of 200 mg orally.	Biguanides	4-14	interleukin 17F	Homo sapiens	81-85
6996339-0	1980	[The effect of biguanides on insulin sensitivity of maturity onset diabetics (author"s transl)].	Biguanides	15-25	insulin	Homo sapiens	29-36
6996339-1	1980	The effect of short-term treatment with biguanides on the insulin sensitivity (KITT) of maturity onset diabetics was tested by means of an insulin tolerance test.	Biguanides	40-50	insulin	Homo sapiens	58-65
6996339-1	1980	The effect of short-term treatment with biguanides on the insulin sensitivity (KITT) of maturity onset diabetics was tested by means of an insulin tolerance test.	Biguanides	40-50	insulin	Homo sapiens	139-146
6996339-4	1980	After three days of biguanide treatment, a highly significant (p less than 0.001) increase in insulin sensitivity was noted in the group of biguanide responders, which was significantly (p less than 0.02) correlated with their previous blood glucose response to long-term biguanide therapy.	Biguanides	20-29	insulin	Homo sapiens	94-101
6996339-4	1980	After three days of biguanide treatment, a highly significant (p less than 0.001) increase in insulin sensitivity was noted in the group of biguanide responders, which was significantly (p less than 0.02) correlated with their previous blood glucose response to long-term biguanide therapy.	Biguanides	140-149	insulin	Homo sapiens	94-101
6996339-4	1980	After three days of biguanide treatment, a highly significant (p less than 0.001) increase in insulin sensitivity was noted in the group of biguanide responders, which was significantly (p less than 0.02) correlated with their previous blood glucose response to long-term biguanide therapy.	Biguanides	140-149	insulin	Homo sapiens	94-101
6996339-6	1980	It is suggested that the blood glucose lowering action of biguanides is due, at least in a definite group of patients with maturity onset diabetes, to a reduction of insulin resistance.	Biguanides	58-68	insulin	Homo sapiens	166-173
6987125-1	1980	The effect of the hypoglycemic biguanide, phenformin, on the binding of insulin to MCF-7 cells, an in vitro line derived from a human breast cancer, has been investigated.	Biguanides	31-40	insulin	Homo sapiens	72-79
404205-6	1977	Serum insulin concentration was higher on glibenclamide than with either biguanide.	Biguanides	73-82	insulin	Homo sapiens	6-13
930174-4	1977	Apart from these investigations the half-life periods of insulin in obese diabetics were established before and after the treatment with biguanides and compared with the half-life period in diabetics treated with insulin.	Biguanides	137-147	insulin	Homo sapiens	57-64
992981-0	1976	Comparison of the effect of parenteral with oral biguanide therapy on vitamin B12 and bile acid absorption.	Biguanides	49-58	NADH:ubiquinone oxidoreductase subunit B3	Homo sapiens	78-81
5598247-0	1967	[Combined insulin-biguanide treatment in diabetic children].	Biguanides	18-27	insulin	Homo sapiens	10-17
1174071-3	1975	Antibodies to the biguanide group were obtained by immunizing rabbits with p-carboxy-phenethyl-biguanide coupled to bovine serum albumin.	Biguanides	18-27	albumin	Oryctolagus cuniculus	123-136
5082058-0	1972	[Interaction of biguanides and exogenous insulin.	Biguanides	16-26	insulin	Homo sapiens	41-48
5563103-0	1971	[Familial primary vasopressin resistant diabetes insipidus sensitive to biguanide].	Biguanides	72-81	arginine vasopressin	Homo sapiens	18-29
4995366-0	1971	[Experimental demonstration of the simulating action of biguanides (phenformin, metformin) on insulin secretion].	Biguanides	56-66	insulin	Homo sapiens	94-101
5519048-0	1970	[Oral antidiabetic monotherapy and combination treatment with glybenclamide (HB 419) and biguanides of insulin receiving diabetics of the adult type].	Biguanides	89-99	insulin	Homo sapiens	103-110
5241471-0	1968	The effects of biguanides on the reactions of thrombin and on the 1-stage prothrombin time of standard human plasma.	Biguanides	15-25	coagulation factor II, thrombin	Homo sapiens	46-54
33686239-3	2021	We hypothesized that resistance to ETC inhibitors from the biguanide class could be induced by inactivation of SMAD4, an important tumor suppressor involved in transforming growth factor beta (TGFbeta) signaling, and associated with altered mitochondrial activity.	Biguanides	59-68	SMAD family member 4	Homo sapiens	111-116
13630685-0	1959	Preliminary clinical observations on the use of a biguanide (DBI) as an oral hypoglycemic agent.	Biguanides	50-59	diazepam binding inhibitor, acyl-CoA binding protein	Homo sapiens	61-64
33686239-3	2021	We hypothesized that resistance to ETC inhibitors from the biguanide class could be induced by inactivation of SMAD4, an important tumor suppressor involved in transforming growth factor beta (TGFbeta) signaling, and associated with altered mitochondrial activity.	Biguanides	59-68	tumor necrosis factor	Homo sapiens	160-191
33686239-3	2021	We hypothesized that resistance to ETC inhibitors from the biguanide class could be induced by inactivation of SMAD4, an important tumor suppressor involved in transforming growth factor beta (TGFbeta) signaling, and associated with altered mitochondrial activity.	Biguanides	59-68	transforming growth factor alpha	Homo sapiens	193-200
33686239-4	2021	Here we show that, paradoxically, both TGFbeta-treatment and the loss of SMAD4, a downstream member of TGFbeta signaling cascade, induce resistance to biguanides, decrease mitochondrial respiration, and fragment the mitochondrial network.	Biguanides	151-161	transforming growth factor alpha	Homo sapiens	39-46
33686239-4	2021	Here we show that, paradoxically, both TGFbeta-treatment and the loss of SMAD4, a downstream member of TGFbeta signaling cascade, induce resistance to biguanides, decrease mitochondrial respiration, and fragment the mitochondrial network.	Biguanides	151-161	SMAD family member 4	Homo sapiens	73-78
33686239-4	2021	Here we show that, paradoxically, both TGFbeta-treatment and the loss of SMAD4, a downstream member of TGFbeta signaling cascade, induce resistance to biguanides, decrease mitochondrial respiration, and fragment the mitochondrial network.	Biguanides	151-161	transforming growth factor alpha	Homo sapiens	103-110
33477154-3	2022	Metformin, a biguanide widely used in the treatment of diabetes mellitus, has been shown to reduce prolactin secretion in various pituitary tumor cell lineages both in vitro and in vivo and in human pituitary adenomas in vitro.	Biguanides	13-22	prolactin	Homo sapiens	99-108
33690729-5	2021	Metformin is an insulin-sensitizing biguanide drug, commonly used in the treatment of type II diabetes mellitus, especially in obese patients.	Biguanides	36-45	insulin	Homo sapiens	16-23
33649449-5	2021	Additionally, the protein expression of HIF-1alpha induced by hypoxia and of GRP78 and GRP94 induced by glucose starvation was markedly suppressed by the biguanides, thereby inhibiting angiogenesis.	Biguanides	154-164	hypoxia inducible factor 1 subunit alpha	Homo sapiens	40-50
33649449-5	2021	Additionally, the protein expression of HIF-1alpha induced by hypoxia and of GRP78 and GRP94 induced by glucose starvation was markedly suppressed by the biguanides, thereby inhibiting angiogenesis.	Biguanides	154-164	heat shock protein family A (Hsp70) member 5	Homo sapiens	77-82
33649449-5	2021	Additionally, the protein expression of HIF-1alpha induced by hypoxia and of GRP78 and GRP94 induced by glucose starvation was markedly suppressed by the biguanides, thereby inhibiting angiogenesis.	Biguanides	154-164	heat shock protein 90 beta family member 1	Homo sapiens	87-92
32678912-4	2020	IgE to the biguanide and/or hexamethylene structure was investigated with PHMB ImmunoCAP (n=32) and by basophil activation tests (BAT) with CHX and ALX (n=37).	Biguanides	11-20	immunoglobulin heavy constant epsilon	Homo sapiens	0-3
32678912-13	2020	IgE-reactivities with the biguanide or hexamethylene components of other disinfectants (ALX, PHMB) can be detected by SPT, PHMB-ImmunoCAP and ALX-BAT in 15-33% of CHX allergic patients.	Biguanides	26-35	immunoglobulin heavy constant epsilon	Homo sapiens	0-3
32678912-0	2020	IgE mediated chlorhexidine allergy - cross-reactivity with other biguanide disinfectants.	Biguanides	65-74	immunoglobulin heavy constant epsilon	Homo sapiens	0-3
32893983-11	2020	Cyclic PIP synthesis is activated by biguanides as metformin two to four-fold and by antihypertensive drugs two-fold.	Biguanides	37-47	prolactin induced protein	Rattus norvegicus	7-10
32312081-8	2020	Furthermore, CBA-Bu could activate AMPK and inhibit mTOR pathways in U87 MG cells, a mechanism involved in the antitumor effect of biguanides.	Biguanides	131-141	mechanistic target of rapamycin kinase	Homo sapiens	52-56
32313883-8	2020	Another class of drug, biguanides, can also inhibit mTOR, but have no lung toxicity.	Biguanides	23-33	mechanistic target of rapamycin kinase	Homo sapiens	52-56
32504219-11	2020	Those receiving first-line dipeptidyl peptidase 4 inhibitors were more likely to receive second-line biguanides and vice versa.	Biguanides	101-111	dipeptidyl peptidase 4	Homo sapiens	27-49
32478334-0	2020	Repression of LKB1 by miR-17~92 Sensitizes MYC-Dependent Lymphoma to Biguanide Treatment.	Biguanides	69-78	serine/threonine kinase 11	Homo sapiens	14-18
32478334-0	2020	Repression of LKB1 by miR-17~92 Sensitizes MYC-Dependent Lymphoma to Biguanide Treatment.	Biguanides	69-78	miR-17-92a-1 cluster host gene	Homo sapiens	22-31
32478334-0	2020	Repression of LKB1 by miR-17~92 Sensitizes MYC-Dependent Lymphoma to Biguanide Treatment.	Biguanides	69-78	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	43-46
32478334-3	2020	Here, we demonstrate that miRNA-mediated silencing of LKB1 confers sensitivity of lymphoma cells to mitochondrial inhibition by biguanides.	Biguanides	128-138	serine/threonine kinase 11	Homo sapiens	54-58
32478334-4	2020	Using both classic (phenformin) and newly developed (IM156) biguanides, we demonstrate that elevated miR-17~92 expression in Myc + lymphoma cells promotes increased apoptosis to biguanide treatment in vitro and in vivo.	Biguanides	60-70	miR-17-92a-1 cluster host gene	Homo sapiens	101-110
32478334-4	2020	Using both classic (phenformin) and newly developed (IM156) biguanides, we demonstrate that elevated miR-17~92 expression in Myc + lymphoma cells promotes increased apoptosis to biguanide treatment in vitro and in vivo.	Biguanides	60-69	miR-17-92a-1 cluster host gene	Homo sapiens	101-110
32478334-6	2020	Mechanistically, biguanide treatment induces metabolic stress in Myc + lymphoma cells by inhibiting TCA cycle metabolism and mitochondrial respiration, exposing metabolic vulnerability.	Biguanides	17-26	MYC proto-oncogene, bHLH transcription factor	Homo sapiens	65-68
32478334-8	2020	Our results identify miR-17~92 expression as a potential biomarker for biguanide sensitivity in malignancies.	Biguanides	71-80	miR-17-92a-1 cluster host gene	Homo sapiens	21-30
31863638-0	2020	Biguanides in combination with olaparib limits tumorigenesis of drug-resistant ovarian cancer cells through inhibition of Snail.	Biguanides	0-10	snail family transcriptional repressor 1	Homo sapiens	122-127
32224876-7	2020	Both biguanides significantly reduced UUO-induced kidney injury, as illustrated by a reduction in KIM-1 protein expression.	Biguanides	5-15	hepatitis A virus cellular receptor 1	Mus musculus	98-103
32158247-11	2020	Results: Using human primary sebocytes, we found that biguanides, isotretinoin and azithromycin induced an acute dose and time-dependent increase in [14C]-acetate labeling of neutral lipids, while AICAR, an AMPK activator, inhibited this DNL response.	Biguanides	54-64	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	207-211
32158247-13	2020	Treatment with biguanides, but not isotretinoin, significantly upregulated ACSS2 gene expression in primary sebocytes and showed synergism with lipogenic activators to induce DNL genes.	Biguanides	15-25	acyl-CoA synthetase short chain family member 2	Homo sapiens	75-80
32049007-5	2020	Because ablation of CtBP2 abrogates the therapeutic effect of phenformin in mice, these data illustrate a biguanide-mediated redox/corepressor interplay, which may represent a relevant target for tumor therapy.	Biguanides	106-115	C-terminal binding protein 2	Mus musculus	20-25
31801069-0	2019	Metabolic Rewiring in Response to Biguanides Is Mediated by mROS/HIF-1a in Malignant Lymphocytes.	Biguanides	34-44	hypoxia inducible factor 1 subunit alpha	Homo sapiens	65-71
31567175-1	2020	BACKGROUND: Since the discovery of insulin, it was the only drug available for the treatment of diabetes until the development of sulfonylureas and biguanides 50 years later.	Biguanides	148-158	insulin	Homo sapiens	35-42
31801069-7	2019	Our results identify HIF-1a signaling as a critical factor in resistance against biguanide-induced mitochondrial dysfunction, allowing selective targeting of metabolic pathways in leukemia and lymphoma.	Biguanides	81-90	hypoxia inducible factor 1 subunit alpha	Homo sapiens	21-27
31550733-2	2019	The aim of the work was to study the possibilities of enhancing the therapeutic effect of anti-estrogen drug toremifene by combining it with biguanide, metformin, on the HER2-positive breast cancer model in FVB/N HER-2/neu transgenic mouse.	Biguanides	141-150	erb-b2 receptor tyrosine kinase 2	Mus musculus	170-174
31316549-3	2019	After demonstrating the efficacy of the biguanide metformin (a PGC-1alpha activator) in a cell model of DS, we extended the study to other molecules that regulate the PGC-1alpha pathway acting on PPAR genes.	Biguanides	40-49	PPARG coactivator 1 alpha	Sus scrofa	63-73
31748231-2	2019	By targeting a druggable transmembrane cavity using a structure-based drug design approach, we discovered a biguanide compound, CHET3, as a highly selective allosteric activator for TASK-3-containing K2P channels, including TASK-3 homomers and TASK-3/TASK-1 heteromers.	Biguanides	108-117	keratin 76	Homo sapiens	200-203
31628595-8	2019	Around half of SGLT2i initiators used dipeptidyl peptidase 4 inhibitors and/or biguanides before using SGLT2i or concomitantly with SGLT2i.	Biguanides	79-89	solute carrier family 5 member 2	Homo sapiens	15-20
33455222-6	2019	LysMET showed similar efficacy to MET in the induction of HT-29 tumor suppression, indicating the importance of the biguanide moiety.	Biguanides	116-125	SAFB like transcription modulator	Homo sapiens	3-6
31238045-5	2019	Testing on P2X1 receptors, resulted in a series of biguanide compounds that yielded a maximum IC50 of 100 muM, but no consistent SAR could be found.	Biguanides	51-60	purinergic receptor P2X 1	Homo sapiens	11-15
30860580-0	2019	Biguanides Exert Antitumoral Actions in Pituitary Tumor Cells Through AMPK-Dependent and -Independent Mechanisms.	Biguanides	0-10	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	70-74
30860580-11	2019	Effects of biguanides on PitNETs could involve the modulation of AMP-activated protein kinase-dependent ([Ca2+]i, PI3K/Akt) and independent (MAPK) mechanisms.	Biguanides	11-21	AKT serine/threonine kinase 1	Homo sapiens	119-122
31288625-6	2019	Genetic studies of the role of AMPK in mouse cancer suggest that, before disease arises, AMPK acts as a tumour suppressor that protects against cancer, with this protection being further enhanced by AMPK activators such as the biguanide phenformin.	Biguanides	227-236	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	31-35
31288625-6	2019	Genetic studies of the role of AMPK in mouse cancer suggest that, before disease arises, AMPK acts as a tumour suppressor that protects against cancer, with this protection being further enhanced by AMPK activators such as the biguanide phenformin.	Biguanides	227-236	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	89-93
31288625-6	2019	Genetic studies of the role of AMPK in mouse cancer suggest that, before disease arises, AMPK acts as a tumour suppressor that protects against cancer, with this protection being further enhanced by AMPK activators such as the biguanide phenformin.	Biguanides	227-236	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	89-93
30918838-10	2019	Recently, drugs belonging to the biguanide class (including metformin) were reported to selectively inhibit CLIC1 activity in CSCs, impairing their viability and invasiveness, but sparing normal stem cells, thus representing potential novel antitumor drugs with a safe toxicological profile.	Biguanides	33-42	chloride intracellular channel 1	Homo sapiens	108-113
31042624-2	2019	Metformin, one of the biguanides used for the treatment of diabetes, is also known to reduce the risk of cancer development and cancer stem-like cells (CSCs), including the expression of CD133.	Biguanides	22-32	prominin 1	Homo sapiens	187-192
30995468-2	2019	AMPK is activated by biguanides, such as metformin and phenformin, and metformin use in diabetics has been associated with reduced cancer risk.	Biguanides	21-31	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
30459716-7	2018	Enzymatic assays confirmed that the net biochemical effect of metformin and other biguanides such as a phenformin was to improve the catalytic efficiency of SIRT1 operating in conditions of low NAD+ in vitro.	Biguanides	82-92	sirtuin 1	Homo sapiens	157-162
30244971-0	2018	Translational and HIF-1alpha-Dependent Metabolic Reprogramming Underpin Metabolic Plasticity and Responses to Kinase Inhibitors and Biguanides.	Biguanides	132-142	hypoxia inducible factor 1 subunit alpha	Homo sapiens	18-28
30244971-4	2018	The mTORC1/4E-BP axis regulates aspartate, asparagine, and serine synthesis by modulating mRNA translation, while ablation of 4E-BP1/2 substantially decreases sensitivity of breast cancer and melanoma cells to KI/biguanide combinations.	Biguanides	213-222	CREB regulated transcription coactivator 1	Mus musculus	4-10
30244971-4	2018	The mTORC1/4E-BP axis regulates aspartate, asparagine, and serine synthesis by modulating mRNA translation, while ablation of 4E-BP1/2 substantially decreases sensitivity of breast cancer and melanoma cells to KI/biguanide combinations.	Biguanides	213-222	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	126-132
30244971-5	2018	Efficacy of the KI/biguanide combinations is also determined by HIF-1alpha-dependent perturbations in glutamine metabolism, which were observed in VHL-deficient renal cancer cells.	Biguanides	19-28	hypoxia inducible factor 1 subunit alpha	Homo sapiens	64-74
29930100-9	2018	Genetic inhibition of ShcA signaling in the Polyoma virus middle T (MT) breast cancer mouse model sensitized mammary tumors to biguanides during the earliest stages of breast cancer progression.	Biguanides	127-137	src homology 2 domain-containing transforming protein C1	Mus musculus	22-26
30328521-4	2018	Trials with insulin sensitizing therapies, including biguanides and thiazolidinediones, have provided inconsistent results on lipid lowering in people with and without diabetes.	Biguanides	53-63	insulin	Homo sapiens	12-19
29862627-9	2018	CONCLUSIONS: While human fat cells primarily express three biguanide transporters, our data suggest that PMAT is the primary target for development of fat cell-specific antilipolytic biguanides with high sensitivity and potency.	Biguanides	183-193	solute carrier family 29 member 4	Homo sapiens	105-109
30205369-8	2018	These biguanide actions are likely mediated through modulation of: 1) common (mTOR/PI3K/intracellular-Ca2+mobilization) and distinct (MAPK) signaling pathways; and 2) gene expression of key receptors regulating somatotrope/corticotrope/gonadotrope function (i.e. upregulation of SSTR2/SSTR5/INSR/IGF1R/LEPR).	Biguanides	6-15	mechanistic target of rapamycin kinase	Homo sapiens	78-82
30066055-4	2018	Recently, the diabetes drug metformin was found to inhibit CYP AA epoxygenase activity, allowing the design of more potent biguanides to target tumor growth.	Biguanides	123-133	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	59-62
30066055-5	2018	Biguanide inhibition of EET synthesis suppresses STAT3 and mTOR pathways, as well as the ETC.	Biguanides	0-9	signal transducer and activator of transcription 3	Homo sapiens	49-54
30066055-5	2018	Biguanide inhibition of EET synthesis suppresses STAT3 and mTOR pathways, as well as the ETC.	Biguanides	0-9	mechanistic target of rapamycin kinase	Homo sapiens	59-63
28565889-2	2018	It belongs to the biguanide class of drugs and it improves hepatic insulin resistance and enhances GLP-1 and peptide YY secretion.	Biguanides	18-27	glucagon like peptide 1 receptor	Homo sapiens	99-104
30186163-0	2018	Inhibition of Chloride Intracellular Channel 1 (CLIC1) as Biguanide Class-Effect to Impair Human Glioblastoma Stem Cell Viability.	Biguanides	58-67	chloride intracellular channel 1	Homo sapiens	14-46
30186163-0	2018	Inhibition of Chloride Intracellular Channel 1 (CLIC1) as Biguanide Class-Effect to Impair Human Glioblastoma Stem Cell Viability.	Biguanides	58-67	chloride intracellular channel 1	Homo sapiens	48-53
30186163-7	2018	All biguanides inhibited CLIC1-mediated ion current, showing the same potency observed in the antiproliferative effects, with the exception of proguanil which was ineffective.	Biguanides	4-14	chloride intracellular channel 1	Homo sapiens	25-30
30186163-10	2018	In conclusion, the inhibition of CLIC1 activity represents a biguanide class-effect to impair GSC viability, invasiveness, and self-renewal, although dissimilarities among different drugs were observed as far as potency, efficacy and selectivity as CLIC1 inhibitors.	Biguanides	61-70	chloride intracellular channel 1	Homo sapiens	33-38
29691292-8	2018	However, more strikingly, pretreatment with phenformin sensitized tumors to dual inhibition of mTOR, leading to a dramatic improvement in survival.Conclusions: Treatment of HCC cells in vitro with the biguanide phenformin causes a metabolic shift to glycolysis, mitochondrial dysfunction and fragmentation, and dramatically sensitizes orthotopic liver tumors to dual inhibition of mTOR.	Biguanides	201-210	mechanistic target of rapamycin kinase	Homo sapiens	95-99
29691292-8	2018	However, more strikingly, pretreatment with phenformin sensitized tumors to dual inhibition of mTOR, leading to a dramatic improvement in survival.Conclusions: Treatment of HCC cells in vitro with the biguanide phenformin causes a metabolic shift to glycolysis, mitochondrial dysfunction and fragmentation, and dramatically sensitizes orthotopic liver tumors to dual inhibition of mTOR.	Biguanides	201-210	mechanistic target of rapamycin kinase	Homo sapiens	381-385
30279304-10	2018	AMPK activator, biguanide metformin, either alone or in combination with other drugs, may selectively modulate signaling pathways, expresses the chemopreventive potential and can be used in current anti-cancer approaches.	Biguanides	16-25	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	0-4
32055553-1	2018	Metformin, an oral hypoglycemic agent belonging to biguanide class, is widely used to treat type 2 diabetes mellitus, and several drug transporters such as organic cation transporters (OCTs), multidrug and toxin extrusion transporter (MATE), and plasma membrane monoamine transporter (PMAT) are thought to affect its disposition.	Biguanides	51-60	solute carrier family 29 member 4	Homo sapiens	246-283
32055553-1	2018	Metformin, an oral hypoglycemic agent belonging to biguanide class, is widely used to treat type 2 diabetes mellitus, and several drug transporters such as organic cation transporters (OCTs), multidrug and toxin extrusion transporter (MATE), and plasma membrane monoamine transporter (PMAT) are thought to affect its disposition.	Biguanides	51-60	solute carrier family 29 member 4	Homo sapiens	285-289
29407948-0	2018	Rational design, chemical synthesis and biological evaluation of novel biguanides exploring species-specificity responsiveness of TAAR1 agonists.	Biguanides	71-81	trace amine associated receptor 1	Homo sapiens	130-135
29447230-8	2018	We also found that a predisposition to mitochondrial dysfunction, caused by a genetic mutation or pharmacological suppression of the electron transport chain by biguanides such as metformin and phenformin, promoted propofol-induced caspase activation and cell death induced by clinical relevant concentrations of propofol in not more than 25 muM.	Biguanides	161-171	latexin	Homo sapiens	342-345
30205369-8	2018	These biguanide actions are likely mediated through modulation of: 1) common (mTOR/PI3K/intracellular-Ca2+mobilization) and distinct (MAPK) signaling pathways; and 2) gene expression of key receptors regulating somatotrope/corticotrope/gonadotrope function (i.e. upregulation of SSTR2/SSTR5/INSR/IGF1R/LEPR).	Biguanides	6-15	somatostatin receptor 2	Homo sapiens	279-284
30205369-8	2018	These biguanide actions are likely mediated through modulation of: 1) common (mTOR/PI3K/intracellular-Ca2+mobilization) and distinct (MAPK) signaling pathways; and 2) gene expression of key receptors regulating somatotrope/corticotrope/gonadotrope function (i.e. upregulation of SSTR2/SSTR5/INSR/IGF1R/LEPR).	Biguanides	6-15	somatostatin receptor 5	Homo sapiens	285-290
30205369-8	2018	These biguanide actions are likely mediated through modulation of: 1) common (mTOR/PI3K/intracellular-Ca2+mobilization) and distinct (MAPK) signaling pathways; and 2) gene expression of key receptors regulating somatotrope/corticotrope/gonadotrope function (i.e. upregulation of SSTR2/SSTR5/INSR/IGF1R/LEPR).	Biguanides	6-15	insulin receptor	Homo sapiens	291-295
30205369-8	2018	These biguanide actions are likely mediated through modulation of: 1) common (mTOR/PI3K/intracellular-Ca2+mobilization) and distinct (MAPK) signaling pathways; and 2) gene expression of key receptors regulating somatotrope/corticotrope/gonadotrope function (i.e. upregulation of SSTR2/SSTR5/INSR/IGF1R/LEPR).	Biguanides	6-15	insulin like growth factor 1 receptor	Homo sapiens	296-301
30205369-8	2018	These biguanide actions are likely mediated through modulation of: 1) common (mTOR/PI3K/intracellular-Ca2+mobilization) and distinct (MAPK) signaling pathways; and 2) gene expression of key receptors regulating somatotrope/corticotrope/gonadotrope function (i.e. upregulation of SSTR2/SSTR5/INSR/IGF1R/LEPR).	Biguanides	6-15	leptin receptor	Homo sapiens	302-306
29480485-5	2018	Two different compounds, AICAr and the biguanide phenformin, were used to promote AMPK activation.	Biguanides	39-48	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	82-86
29053951-0	2017	Heme Binding Biguanides Target Cytochrome P450-Dependent Cancer Cell Mitochondria.	Biguanides	13-23	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	31-46
28988825-5	2017	Pro-metastatic capabilities of PGC-1alpha are linked to enhanced global bioenergetic capacity, facilitating the ability to cope with bioenergetic disruptors like biguanides.	Biguanides	162-172	PPARG coactivator 1 alpha	Sus scrofa	31-41
28919040-0	2017	Heme Binding Biguanides Target Cytochrome P450-Dependent Cancer Cell Mitochondria.	Biguanides	13-23	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	31-46
28919040-5	2017	Metformin bound to the active-site heme of CYP3A4 in a co-crystal structure, establishing CYP3A4 as a biguanide target.	Biguanides	102-111	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	43-49
29553076-7	2018	Meanwhile, Glucagon-like peptide-1 (GLP-1) receptor agonist, thiazolidine, biguanide and Dipeptidyl peptidase-4 (DPP-4) inhibitor have an effect of protecting vascular endothelial function beyond glycemic control.	Biguanides	75-84	glucagon	Homo sapiens	11-34
28919040-9	2017	CYP3A4 AA epoxygenase inhibition by biguanides thus demonstrates convergence between eicosanoid activity in mitochondria and biguanide action in cancer, opening a new avenue for cancer drug discovery.	Biguanides	36-46	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	0-6
28919040-9	2017	CYP3A4 AA epoxygenase inhibition by biguanides thus demonstrates convergence between eicosanoid activity in mitochondria and biguanide action in cancer, opening a new avenue for cancer drug discovery.	Biguanides	36-45	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	0-6
28919040-5	2017	Metformin bound to the active-site heme of CYP3A4 in a co-crystal structure, establishing CYP3A4 as a biguanide target.	Biguanides	102-111	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	90-96
27549920-9	2017	As a second OHA added to the first OHA during the first 2 years, dipeptidyl peptidase-4 inhibitors were chosen most often, especially if a biguanide was the first OHA.	Biguanides	139-148	dipeptidyl peptidase 4	Homo sapiens	65-87
28387573-3	2017	Here we report that the biguanide metformin prevents BRCA1 haploinsufficiency-driven RANKL gene overexpression, thereby disrupting an auto-regulatory feedback control of RANKL-addicted cancer stem cell-like states within BRCA1mut/- cell populations.	Biguanides	24-33	BRCA1 DNA repair associated	Homo sapiens	53-58
28387573-3	2017	Here we report that the biguanide metformin prevents BRCA1 haploinsufficiency-driven RANKL gene overexpression, thereby disrupting an auto-regulatory feedback control of RANKL-addicted cancer stem cell-like states within BRCA1mut/- cell populations.	Biguanides	24-33	TNF superfamily member 11	Homo sapiens	85-90
28387573-3	2017	Here we report that the biguanide metformin prevents BRCA1 haploinsufficiency-driven RANKL gene overexpression, thereby disrupting an auto-regulatory feedback control of RANKL-addicted cancer stem cell-like states within BRCA1mut/- cell populations.	Biguanides	24-33	BRCA1 DNA repair associated	Homo sapiens	221-226
28766937-3	2017	Motivated by the growing recognition that anti-diabetic biguanides may act directly upon the gut microbiome, we have determined structures of the complexes formed between the anti-diabetic biguanides (phenformin, buformin, and metformin) and Escherichia coli dihydrofolate reductase (ecDHFR) based on nuclear magnetic resonance, crystallographic, and molecular modeling studies.	Biguanides	56-66	dihydrofolate reductase	Escherichia coli	284-290
28766937-3	2017	Motivated by the growing recognition that anti-diabetic biguanides may act directly upon the gut microbiome, we have determined structures of the complexes formed between the anti-diabetic biguanides (phenformin, buformin, and metformin) and Escherichia coli dihydrofolate reductase (ecDHFR) based on nuclear magnetic resonance, crystallographic, and molecular modeling studies.	Biguanides	189-199	dihydrofolate reductase	Escherichia coli	284-290
28766937-5	2017	The biguanides competitively inhibit the activity of ecDHFR, with the phenformin inhibition constant being 100-fold lower than that of metformin.	Biguanides	4-14	dihydrofolate reductase	Escherichia coli	53-59
28699756-0	2017	Incorporation of a Biguanide Scaffold Enhances Drug Uptake by Organic Cation Transporters 1 and 2.	Biguanides	19-28	solute carrier family 22 member 1	Homo sapiens	62-97
28699756-3	2017	In this study, we demonstrate that inclusion of a biguanide functionality can potentiate uptake by the organic cation transporters 1 and 2 (OCT1 and OCT2).	Biguanides	50-59	solute carrier family 22 member 1	Homo sapiens	103-138
28699756-3	2017	In this study, we demonstrate that inclusion of a biguanide functionality can potentiate uptake by the organic cation transporters 1 and 2 (OCT1 and OCT2).	Biguanides	50-59	solute carrier family 22 member 1	Homo sapiens	140-144
28699756-3	2017	In this study, we demonstrate that inclusion of a biguanide functionality can potentiate uptake by the organic cation transporters 1 and 2 (OCT1 and OCT2).	Biguanides	50-59	solute carrier family 22 member 2	Homo sapiens	149-153
28699756-5	2017	Our results show that addition of the biguanide significantly improved OCT1- and OCT2-mediated transport for the majority of compounds.	Biguanides	38-47	solute carrier family 22 member 1	Homo sapiens	71-75
28699756-5	2017	Our results show that addition of the biguanide significantly improved OCT1- and OCT2-mediated transport for the majority of compounds.	Biguanides	38-47	solute carrier family 22 member 2	Homo sapiens	81-85
28699756-9	2017	Taken together, we conclude that the inclusion of the biguanide scaffold in nonsubstrates of OCT1 and OCT2 increase their propensity to become substrates and inhibitors for these transporters.	Biguanides	54-63	solute carrier family 22 member 1	Homo sapiens	93-97
28699756-9	2017	Taken together, we conclude that the inclusion of the biguanide scaffold in nonsubstrates of OCT1 and OCT2 increase their propensity to become substrates and inhibitors for these transporters.	Biguanides	54-63	solute carrier family 22 member 2	Homo sapiens	102-106
28337254-8	2017	Biguanides can be used to activate AMPK, but AMPK activity is modified by many different interacting factors; understanding these factors is important in order to control the abnormal growth processes that lead to breast cancer neoplasia.	Biguanides	0-10	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	35-39
27929708-0	2017	NBR2-GLUT1 axis regulates cancer cell sensitivity to biguanides.	Biguanides	53-63	neighbor of BRCA1 lncRNA 2	Homo sapiens	0-4
27823885-0	2017	Novel biguanide-based derivatives scouted as TAAR1 agonists: Synthesis, biological evaluation, ADME prediction and molecular docking studies.	Biguanides	6-15	trace amine-associated receptor 1	Mus musculus	45-50
27929708-0	2017	NBR2-GLUT1 axis regulates cancer cell sensitivity to biguanides.	Biguanides	53-63	solute carrier family 2 member 1	Homo sapiens	5-10
27984722-5	2016	Biguanide-induced inactivation of mTORC1 subsequently inhibits growth through transcriptional induction of ACAD10.	Biguanides	0-9	CREB regulated transcription coactivator 1	Mus musculus	34-40
28770024-9	2017	In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future.	Biguanides	40-50	acetylcholinesterase (Cartwright blood group)	Homo sapiens	91-95
27655410-1	2016	BACKGROUND: NT1014 is a novel biguanide and AMPK activator with a high affinity for the organic cation-specific transporters, OCT1 and OCT3.	Biguanides	30-39	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	126-130
27599468-3	2016	The biguanide metformin is reported to prevent transforming growth factor-beta (TGF-beta)-induced EMT and proliferation of cancer.	Biguanides	4-13	transforming growth factor beta 1	Homo sapiens	47-78
27599468-3	2016	The biguanide metformin is reported to prevent transforming growth factor-beta (TGF-beta)-induced EMT and proliferation of cancer.	Biguanides	4-13	transforming growth factor beta 1	Homo sapiens	80-88
27655410-1	2016	BACKGROUND: NT1014 is a novel biguanide and AMPK activator with a high affinity for the organic cation-specific transporters, OCT1 and OCT3.	Biguanides	30-39	solute carrier family 22 (organic cation transporter), member 3	Mus musculus	135-139
26986624-6	2016	Taken together, the data presented here suggest biguanides and ARBs have a beneficial effect on the vasculature by the cascade of AMPK phosphorylation of PARP1 to inhibit PARP1 activity and protein PARylation in ECs, thereby mitigating endothelial dysfunction.	Biguanides	48-58	protein kinase, AMP-activated, alpha 2 catalytic subunit	Mus musculus	130-134
27564915-1	2016	Ion transfer voltammetry is used to estimate the acid dissociation constants Ka1 and Ka2 of the mono- and diprotonated forms of the biguanide drugs metformin (MF), phenformin (PF), and 1-phenylbiguanide (PB) in an aqueous solution.	Biguanides	132-141	glutamate ionotropic receptor kainate type subunit 4	Homo sapiens	77-80
27564915-1	2016	Ion transfer voltammetry is used to estimate the acid dissociation constants Ka1 and Ka2 of the mono- and diprotonated forms of the biguanide drugs metformin (MF), phenformin (PF), and 1-phenylbiguanide (PB) in an aqueous solution.	Biguanides	132-141	glutamate ionotropic receptor kainate type subunit 5	Homo sapiens	85-88
27564915-3	2016	As a result, the monoprotonated forms of these biguanides should prevail in a considerably broader range of pH 1-15 (MFH(+), PFH(+)) and 2-13 (PBH(+)).	Biguanides	47-57	forkhead box P1	Homo sapiens	117-120
27350110-0	2016	L503F variant of carnitine/organic cation transporter 1 efficiently transports metformin and other biguanides.	Biguanides	99-109	solute carrier family 22 member 4	Homo sapiens	17-55
27350110-1	2016	OBJECTIVES: Carnitine/organic cation transporter 1 (OCTN1) is involved in gastrointestinal absorption and mitochondrial toxicity of biguanides in rodents, but its pharmacokinetic roles in humans are largely unknown.	Biguanides	132-142	solute carrier family 22 member 4	Homo sapiens	12-50
27350110-1	2016	OBJECTIVES: Carnitine/organic cation transporter 1 (OCTN1) is involved in gastrointestinal absorption and mitochondrial toxicity of biguanides in rodents, but its pharmacokinetic roles in humans are largely unknown.	Biguanides	132-142	solute carrier family 22 member 4	Homo sapiens	52-57
27350110-2	2016	The purpose of this study was to clarify the transport activities of two major OCTN1 variants, L503F and I306T, for gabapentin and three biguanide drugs, metformin, buformin and phenformin.	Biguanides	137-146	solute carrier family 22 member 4	Homo sapiens	79-84
27350110-5	2016	Uptake of biguanides, especially metformin, mediated by OCTN1 variant L503F, which is commonly found in Caucasians, was much higher than that by the wild-type transporter (WT-OCTN1).	Biguanides	10-20	solute carrier family 22 member 4	Homo sapiens	56-61
27350110-5	2016	Uptake of biguanides, especially metformin, mediated by OCTN1 variant L503F, which is commonly found in Caucasians, was much higher than that by the wild-type transporter (WT-OCTN1).	Biguanides	10-20	solute carrier family 22 member 4	Homo sapiens	175-180
27259235-6	2016	The anti-diabetic biguanide metformin "reversed" the metabolomic signature and anabolic phenotype of BRCA1 one-hit cells by shutting down mitochondria-driven generation of precursors for lipogenic pathways and reducing the BCAA pool for protein synthesis and TCA fueling.	Biguanides	18-27	BRCA1 DNA repair associated	Homo sapiens	101-106
27259235-6	2016	The anti-diabetic biguanide metformin "reversed" the metabolomic signature and anabolic phenotype of BRCA1 one-hit cells by shutting down mitochondria-driven generation of precursors for lipogenic pathways and reducing the BCAA pool for protein synthesis and TCA fueling.	Biguanides	18-27	AT-rich interaction domain 4B	Homo sapiens	223-227
27283492-3	2016	We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells.	Biguanides	76-85	BCL2 apoptosis regulator	Homo sapiens	150-155
27344367-5	2016	Given its cationic head group, biguanide, DOBP could encapsulate TNF-related apoptosis-inducing ligand (TRAIL) plasmids into Lipid-Protamine-DNA (LPD) nanoparticles (NPs) for systemic gene delivery.	Biguanides	31-40	TNF superfamily member 10	Homo sapiens	65-102
27344367-5	2016	Given its cationic head group, biguanide, DOBP could encapsulate TNF-related apoptosis-inducing ligand (TRAIL) plasmids into Lipid-Protamine-DNA (LPD) nanoparticles (NPs) for systemic gene delivery.	Biguanides	31-40	TNF superfamily member 10	Homo sapiens	104-109
26917452-1	2016	Metformin, an insulin sensitiser from the biguanide family of molecules, is used for the treatment of insulin resistance in type 2 diabetes individuals.	Biguanides	42-51	insulin	Gallus gallus	14-21
26917452-1	2016	Metformin, an insulin sensitiser from the biguanide family of molecules, is used for the treatment of insulin resistance in type 2 diabetes individuals.	Biguanides	42-51	insulin	Gallus gallus	102-109
26986624-6	2016	Taken together, the data presented here suggest biguanides and ARBs have a beneficial effect on the vasculature by the cascade of AMPK phosphorylation of PARP1 to inhibit PARP1 activity and protein PARylation in ECs, thereby mitigating endothelial dysfunction.	Biguanides	48-58	poly (ADP-ribose) polymerase family, member 1	Mus musculus	154-159
26986624-6	2016	Taken together, the data presented here suggest biguanides and ARBs have a beneficial effect on the vasculature by the cascade of AMPK phosphorylation of PARP1 to inhibit PARP1 activity and protein PARylation in ECs, thereby mitigating endothelial dysfunction.	Biguanides	48-58	poly (ADP-ribose) polymerase family, member 1	Mus musculus	171-176
26998043-3	2016	Currently, the first-line treatment of diabetes is based on metformin, which is an inducer of AMP-activated protein kinase (AMPK) and belongs to the biguanide class of pharmaceuticals.	Biguanides	149-158	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	94-122
26998043-3	2016	Currently, the first-line treatment of diabetes is based on metformin, which is an inducer of AMP-activated protein kinase (AMPK) and belongs to the biguanide class of pharmaceuticals.	Biguanides	149-158	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	124-128
30603277-4	2016	The HbA1c level decreased in patients taking BG alone (-2.76 %) and DPP-4i alone (-2.46 %).	Biguanides	45-47	hemoglobin subunit alpha 1	Homo sapiens	4-8
26133123-4	2015	Biguanide drugs which inhibit mitochondrial complex I and repress mTOR signaling are clinically used to treat type 2 diabetes mellitus patients (T2DM) and were recently found to reduce the risk of HCC in T2DM patients.	Biguanides	0-9	mechanistic target of rapamycin kinase	Homo sapiens	66-70
26302449-5	2015	Interestingly, metformin, one of the biguanide drugs that has anti-diabetic effects, attenuated lipotoxicity-induced mesangial cell apoptosis and restored GLP-1R expression.	Biguanides	37-46	glucagon-like peptide 1 receptor	Mus musculus	155-161
26807315-5	2015	The extracellular regulated protein kinases (ERK) signaling is known to be a major cellular target of biguanides.	Biguanides	102-112	mitogen-activated protein kinase 1	Homo sapiens	4-43
26807315-5	2015	The extracellular regulated protein kinases (ERK) signaling is known to be a major cellular target of biguanides.	Biguanides	102-112	mitogen-activated protein kinase 1	Homo sapiens	45-48
26807315-6	2015	Based on KRAS activates several down-stream effectors leading to the stimulation of the RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) and phosphatidylinositol-3-kinase (PI3K) pathways, we investigated the anti-tumor effects of biguanides on the proliferation of KRAS-mutated tumor cells in vitro and on KRAS-driven tumor growth in vivo.	Biguanides	270-280	KRAS proto-oncogene, GTPase	Homo sapiens	9-13
26807315-6	2015	Based on KRAS activates several down-stream effectors leading to the stimulation of the RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) and phosphatidylinositol-3-kinase (PI3K) pathways, we investigated the anti-tumor effects of biguanides on the proliferation of KRAS-mutated tumor cells in vitro and on KRAS-driven tumor growth in vivo.	Biguanides	270-280	zinc fingers and homeoboxes 2	Homo sapiens	88-91
26807315-6	2015	Based on KRAS activates several down-stream effectors leading to the stimulation of the RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) and phosphatidylinositol-3-kinase (PI3K) pathways, we investigated the anti-tumor effects of biguanides on the proliferation of KRAS-mutated tumor cells in vitro and on KRAS-driven tumor growth in vivo.	Biguanides	270-280	zinc fingers and homeoboxes 2	Homo sapiens	164-167
26807315-6	2015	Based on KRAS activates several down-stream effectors leading to the stimulation of the RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) and phosphatidylinositol-3-kinase (PI3K) pathways, we investigated the anti-tumor effects of biguanides on the proliferation of KRAS-mutated tumor cells in vitro and on KRAS-driven tumor growth in vivo.	Biguanides	270-280	mitogen-activated protein kinase kinase 7	Homo sapiens	168-171
26807315-6	2015	Based on KRAS activates several down-stream effectors leading to the stimulation of the RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) and phosphatidylinositol-3-kinase (PI3K) pathways, we investigated the anti-tumor effects of biguanides on the proliferation of KRAS-mutated tumor cells in vitro and on KRAS-driven tumor growth in vivo.	Biguanides	270-280	mitogen-activated protein kinase 1	Homo sapiens	172-175
26807315-6	2015	Based on KRAS activates several down-stream effectors leading to the stimulation of the RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) and phosphatidylinositol-3-kinase (PI3K) pathways, we investigated the anti-tumor effects of biguanides on the proliferation of KRAS-mutated tumor cells in vitro and on KRAS-driven tumor growth in vivo.	Biguanides	270-280	KRAS proto-oncogene, GTPase	Homo sapiens	305-309
26807315-6	2015	Based on KRAS activates several down-stream effectors leading to the stimulation of the RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase (RAF/MEK/ERK) and phosphatidylinositol-3-kinase (PI3K) pathways, we investigated the anti-tumor effects of biguanides on the proliferation of KRAS-mutated tumor cells in vitro and on KRAS-driven tumor growth in vivo.	Biguanides	270-280	KRAS proto-oncogene, GTPase	Homo sapiens	305-309
26276391-4	2015	Importantly, overexpression of Pin1 suppressed AMPK phosphorylation in response to either 2-deoxyglucose or biguanide stimulation, whereas Pin1 knockdown by siRNAs or treatment with Pin1 inhibitors enhanced it.	Biguanides	108-117	peptidyl-prolyl cis/trans isomerase, NIMA-interacting 1	Mus musculus	31-35
26133123-8	2015	The energy metabolism change enhanced AMP-activated protein kinase (AMPK) activation, mTOR repression and downregulation of cyclin D1 and Mcl-1 in response to the mitochondrial inhibitors and biguanides.	Biguanides	192-202	cyclin D1	Homo sapiens	124-133
26133123-8	2015	The energy metabolism change enhanced AMP-activated protein kinase (AMPK) activation, mTOR repression and downregulation of cyclin D1 and Mcl-1 in response to the mitochondrial inhibitors and biguanides.	Biguanides	192-202	MCL1 apoptosis regulator, BCL2 family member	Homo sapiens	138-143
26087341-7	2015	Insulin resistance may be improved among obese individuals with T1DM by biguanides (metformin) and glucagon-like peptide-1 agonists (exenatide).	Biguanides	72-82	insulin	Homo sapiens	0-7
26316711-7	2015	RESULTS: Sulfonylureas in combination (P=0.002) and sulfonylurea monotherapy (P<0.001) were found to be associated with good glycemic control, whereas insulin in combination (P=0.051), and combination biguanides and insulin therapy (P=0.012) were found to be associated with poor glycemic control.	Biguanides	204-214	insulin	Homo sapiens	154-161
25667085-2	2015	This study demonstrates the effect of metformin, a therapeutic biguanide administered for T2DM therapy, on beta-amyloid precursor protein (APP) metabolism in in vitro, ex vivo and in vivo models.	Biguanides	63-72	amyloid beta precursor protein	Homo sapiens	107-137
25980580-8	2015	Targeted metabolomics studies revealed that the ability of metformin to interfere with the anaplerotic entry of glutamine into the tricarboxylic acid cycle could explain the hypersensitivity of IDH1-mutant cells to biguanides.	Biguanides	215-225	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	194-198
25980580-6	2015	The mitochondrial biguanide poisons, metformin and phenformin, further impaired the intrinsic weakness of IDH1-mutant cells to use certain carbon-energy sources.	Biguanides	18-27	isocitrate dehydrogenase (NADP(+)) 1	Homo sapiens	106-110
25328079-1	2015	This study aimed to explore the effects of the dipeptidyl peptidase-4 inhibitor sitagliptin and the biguanide metformin on the secretion of insulin and glucagon, as well as incretin levels, in Japanese subjects with type 2 diabetes mellitus poorly controlled with insulin monotherapy.	Biguanides	100-109	insulin	Homo sapiens	140-147
25894929-0	2015	Disruption of BASIGIN decreases lactic acid export and sensitizes non-small cell lung cancer to biguanides independently of the LKB1 status.	Biguanides	96-106	basigin	Mus musculus	14-21
25894929-9	2015	However, only BSG-null cells, independently of their LKB1 status, remained sensitive to biguanides in hypoxia in vitro and tumour growth in nude mice.	Biguanides	88-98	basigin	Mus musculus	14-17
25196138-6	2015	In vivo, biguanides inhibited local and metastatic growth of triple negative and HER2+ BC in immune-competent and immune-deficient mice orthotopically injected with BC.	Biguanides	9-19	erb-b2 receptor tyrosine kinase 2	Mus musculus	81-85
25196138-7	2015	Biguanides inhibited local and metastatic BC growth in a genetically engineered murine model model of HER2+ BC.	Biguanides	0-10	erb-b2 receptor tyrosine kinase 2	Mus musculus	102-106
26166607-5	2015	This biguanide is an oral insulin-sensitizing agent capable of increasing insulin sensitivity and decreasing plasma fasting insulin levels.	Biguanides	5-14	insulin	Homo sapiens	26-33
26166607-5	2015	This biguanide is an oral insulin-sensitizing agent capable of increasing insulin sensitivity and decreasing plasma fasting insulin levels.	Biguanides	5-14	insulin	Homo sapiens	74-81
26166607-5	2015	This biguanide is an oral insulin-sensitizing agent capable of increasing insulin sensitivity and decreasing plasma fasting insulin levels.	Biguanides	5-14	insulin	Homo sapiens	74-81
25575627-5	2015	Importantly, recent studies showed that the anti-tumorigenic effects of many "indirect" AMPK activators such as anti-diabetic biguanides are not dependent on AMPK; rather the activation of AMPK induces the resistance to their cytotoxic effects, emphasizing the pro-tumorigenic effect of AMPK.	Biguanides	126-136	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	88-92
24961373-7	2014	Metformin and the biguanide analog, phenformin, competitively inhibited OCT1-mediated thiamine uptake.	Biguanides	18-27	solute carrier family 22 (organic cation transporter), member 1	Mus musculus	72-76
25361177-4	2014	Our data with other compounds suggested that biguanides combined with EGFR inhibitors have the potential to outperform other targeted drug combinations and could be employed in other breast cancer subtypes, as well as other tumor types, with activated EGFR and PI3K signaling.	Biguanides	45-55	epidermal growth factor receptor	Homo sapiens	252-256
24531544-7	2014	Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine.	Biguanides	72-81	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	28-32
23889512-2	2014	Current biguanide and thiazolidinedione treatments for type 2 diabetes have a number of clinical limitations, the most serious long-term limitation being the eventual need for insulin replacement therapy (Table 1).	Biguanides	8-17	insulin	Homo sapiens	176-183
24531544-7	2014	Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine.	Biguanides	72-81	nuclear receptor subfamily 1, group H, member 4	Mus musculus	103-106
24531544-7	2014	Furthermore, treatment with AMPK activators, including the antidiabetic biguanide metformin, inhibited FXR agonist induction of FXR target genes in mouse liver and intestine.	Biguanides	72-81	nuclear receptor subfamily 1, group H, member 4	Mus musculus	128-131
24668601-13	2014	Metformin, a biguanide, targets additional mechanisms of hyperglycemia by inhibiting hepatic glucose production and enhancing peripheral glucose uptake and thereby reducing insulin resistance; acarbose reversibly bind to pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolases.	Biguanides	13-22	amylase alpha 2A	Homo sapiens	221-245
24045366-3	2014	We have synthesized numerous guanide, biguanide, phenylguanide, and naphthylguanide compounds that bind to CXCR4 at the CXCL12-binding site and thus should prevent CXCR4-facilitated cancer metastasis.	Biguanides	38-47	chemokine (C-X-C motif) receptor 4	Mus musculus	107-112
24045366-3	2014	We have synthesized numerous guanide, biguanide, phenylguanide, and naphthylguanide compounds that bind to CXCR4 at the CXCL12-binding site and thus should prevent CXCR4-facilitated cancer metastasis.	Biguanides	38-47	chemokine (C-X-C motif) ligand 12	Mus musculus	120-126
24045366-3	2014	We have synthesized numerous guanide, biguanide, phenylguanide, and naphthylguanide compounds that bind to CXCR4 at the CXCL12-binding site and thus should prevent CXCR4-facilitated cancer metastasis.	Biguanides	38-47	chemokine (C-X-C motif) receptor 4	Mus musculus	164-169
24189526-4	2013	Antidiabetic biguanides such as metformin, which reduce hyperglycemia and hyperinsulinemia by decreasing insulin resistance, extend lifespan, and inhibit carcinogenesis in rodents.	Biguanides	13-23	insulin	Homo sapiens	79-86
24577463-3	2014	No study has yet reported a protective cognitive effect of metformin, an insulin-sensitizing biguanide widely used in diabetic patients.	Biguanides	93-102	insulin	Homo sapiens	73-80
23518341-2	2013	Furthermore, Haq and colleagues (also in this issue of Cancer Cell) show situations where increased oxidative phosphorylation is required for melanomas to survive inhibition of B-RAF, suggesting investigation of therapeutic combinations of B-RAF inhibitors with biguanides.	Biguanides	262-272	B-Raf proto-oncogene, serine/threonine kinase	Homo sapiens	177-182
23582785-0	2013	Transport of biguanides by human organic cation transporter OCT2.	Biguanides	13-23	solute carrier family 22 member 2	Homo sapiens	60-64
23582785-6	2013	Both biguanides were found to be good substrates for hOCT2.	Biguanides	5-15	solute carrier family 22 member 2	Homo sapiens	53-58
23582785-9	2013	This is the first report that has compared the transport profiles of these biguanides in hOCT2-expressing oocytes.	Biguanides	75-85	solute carrier family 22 member 2	Homo sapiens	89-94
22861817-1	2013	BACKGROUND: Recent evidence indicates that metformin, a biguanide used as first-line treatment for type 2 diabetes, prevents the conversion of carcinogen-induced oral dysplasias into head and neck squamous cell carcinomas (HNSCC), most likely by inhibiting mammalian target of rapamycin complex 1 (mTORC1) oncogenic signaling.	Biguanides	56-65	CREB regulated transcription coactivator 1	Mus musculus	298-304
22492524-4	2012	Biguanide/metal interactions are stabilized by extensive pi-electron delocalization and by investigating analogs of metformin; we provide evidence that this intrinsic property enables biguanides to regulate AMPK, glucose production, gluconeogenic gene expression, mitochondrial respiration, and mitochondrial copper binding.	Biguanides	0-9	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	207-211
23221006-10	2013	This study was, thus, the first to demonstrate OCTN1-mediated mitochondrial transport and toxicity of biguanide in vivo in rodents.	Biguanides	102-111	solute carrier family 22 (organic cation transporter), member 4	Mus musculus	47-52
23249988-2	2013	HL3 and HL5 have been structurally characterised by X-ray crystallography, which shows them to adopt the expected tautomeric form for biguanides.	Biguanides	134-144	dynein cytoplasmic 1 heavy chain 1	Homo sapiens	0-3
23249988-3	2013	They have extensive hydrogen-bonding interactions in the solid state, involving the biguanide NH groups supported by, in the case of HL3, the OCH3 aryl substituents or, in the case of HL5, Br   Br interactions.	Biguanides	84-93	dynein cytoplasmic 1 heavy chain 1	Homo sapiens	133-136
23410967-2	2013	In this issue of Cancer Cell, Shackelford and colleagues show, paradoxically, that biguanides are more effective in the treatment of mouse tumors that lack a functional LKB1-AMPK pathway.	Biguanides	83-93	serine/threonine kinase 11	Mus musculus	169-173
23631205-5	2013	In drug therapy of such patients, the drugs to improve insulin resistance, such as biguanides, thiazolidine derivatives, DPP-4 inhibitors and GLP-1 analogues should be selected.	Biguanides	83-93	insulin	Homo sapiens	55-62
20455069-4	2012	Some authors suggest that Metformin has no direct inhibitory effect on DPP-4 activity and that Metformin and the other biguanides enhance GLP-1 secretion; others suggest a possible role of Metformin in the inhibition of the DPP-4 activity.	Biguanides	119-129	glucagon	Homo sapiens	138-143
22492524-4	2012	Biguanide/metal interactions are stabilized by extensive pi-electron delocalization and by investigating analogs of metformin; we provide evidence that this intrinsic property enables biguanides to regulate AMPK, glucose production, gluconeogenic gene expression, mitochondrial respiration, and mitochondrial copper binding.	Biguanides	184-194	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	207-211
22492524-5	2012	In contrast, regulation of S6 phosphorylation is prevented only by direct modification of the metal-liganding groups of the biguanide structure, supporting recent data that AMPK and S6 phosphorylation are regulated independently by biguanides.	Biguanides	124-133	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	173-177
22492524-5	2012	In contrast, regulation of S6 phosphorylation is prevented only by direct modification of the metal-liganding groups of the biguanide structure, supporting recent data that AMPK and S6 phosphorylation are regulated independently by biguanides.	Biguanides	232-242	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	173-177
22333578-3	2012	The indirect and direct activation of AMPK with the antidiabetic biguanide metformin and the thienopyridone A-769662, respectively, impeded the reprogramming of mouse embryonic and human diploid fibroblasts into iPSCs.	Biguanides	65-74	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	38-42
21298495-6	2012	Additionally, DM2 patients without cancer, who had parents or siblings with DM2, received biguanide metformin versus sulfonylurea derivatives more often than those with breast or endometrial cancer, either with or without family history of DM2.	Biguanides	90-99	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	14-17
21298495-6	2012	Additionally, DM2 patients without cancer, who had parents or siblings with DM2, received biguanide metformin versus sulfonylurea derivatives more often than those with breast or endometrial cancer, either with or without family history of DM2.	Biguanides	90-99	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	76-79
21298495-6	2012	Additionally, DM2 patients without cancer, who had parents or siblings with DM2, received biguanide metformin versus sulfonylurea derivatives more often than those with breast or endometrial cancer, either with or without family history of DM2.	Biguanides	90-99	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	76-79
22402126-0	2012	Hyperactivation of 4E-binding protein 1 as a mediator of biguanide-induced cytotoxicity during glucose deprivation.	Biguanides	57-66	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	19-39
22402126-5	2012	Importantly, the 4E-BP1 hyperactivation can be also seen in xenografted cancer cells through an in vivo biguanide treatment.	Biguanides	104-113	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	17-23
22402126-6	2012	Our findings indicate that antitumor action of biguanides can be mediated by 4E-BP1 hyperactivation, which results in UPR inhibition and selective cell killing when glucose is withdrawn.	Biguanides	47-57	eukaryotic translation initiation factor 4E binding protein 1	Homo sapiens	77-83
22333588-3	2012	We recently envisioned that intervention strategies aimed at reversing the bioenergetic signature of cancer cells (e.g., the antidiabetic biguanide metformin) should correct oncogene (e.g., HER2)-driven MHC-I defects, thus preventing immune escape of oncogene transformants.	Biguanides	138-147	erb-b2 receptor tyrosine kinase 2	Homo sapiens	190-194
20683653-11	2011	AMP-kinase was stimulated by MF approximately equally in MCF-7, TAM-R, and LTED cells, while inhibition by biguanide of p-S6K as a downstream target of mTOR was strongest in TAM-R cells.	Biguanides	107-116	ribosomal protein S6 kinase B1	Homo sapiens	120-125
21986525-0	2011	Relevance of the OCT1 transporter to the antineoplastic effect of biguanides.	Biguanides	66-76	solute carrier family 22 member 1	Homo sapiens	17-21
21986525-4	2011	We show that siRNA knockdown of OCT1 reduced sensitivity of epithelial ovarian cancer cells to metformin, but interestingly not to another biguanide, phenformin, with respect to both activation of AMP kinase and inhibition of proliferation.	Biguanides	139-148	solute carrier family 22 member 1	Homo sapiens	32-36
23077661-1	2012	The biguanide drug, metformin, commonly used to treat type-2 diabetes, has been shown to extend lifespan and reduce fecundity in C. elegans through a dietary restriction-like mechanism via the AMP-activated protein kinase (AMPK) and the AMPK-activating kinase, LKB1.	Biguanides	4-13	AMP-activated protein kinase alpha subunit	Drosophila melanogaster	223-227
23077661-1	2012	The biguanide drug, metformin, commonly used to treat type-2 diabetes, has been shown to extend lifespan and reduce fecundity in C. elegans through a dietary restriction-like mechanism via the AMP-activated protein kinase (AMPK) and the AMPK-activating kinase, LKB1.	Biguanides	4-13	AMP-activated protein kinase alpha subunit	Drosophila melanogaster	237-241
21717584-1	2011	It has been reported that metformin, a biguanide derivative widely used in type II diabetic patients, has antitumor activities in some cancers by activation of AMP-activated protein kinase (AMPK).	Biguanides	39-48	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	160-188
21717584-1	2011	It has been reported that metformin, a biguanide derivative widely used in type II diabetic patients, has antitumor activities in some cancers by activation of AMP-activated protein kinase (AMPK).	Biguanides	39-48	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	190-194
20683653-11	2011	AMP-kinase was stimulated by MF approximately equally in MCF-7, TAM-R, and LTED cells, while inhibition by biguanide of p-S6K as a downstream target of mTOR was strongest in TAM-R cells.	Biguanides	107-116	mechanistic target of rapamycin kinase	Homo sapiens	152-156
21484577-4	2011	In addition, it is now demonstrated that AMPK is one of the probable (albeit indirect) targets of major antidiabetic drugs drugs including the biguanides (metformin metformin ) and thiazolidinedione thiazolidinedione s, as well as of insulin-sensitizing adipokines (e.g., adiponectin adiponectin ).	Biguanides	143-153	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	41-45
21847455-5	2011	Based on this review, noninsulin pharmacological therapies can be divided into following classes: (1) Insulin-sensitizing agents (biguanides and thiazolidinediones), (2) gastrointestinal nutrient absorption modulators (alpha-Glucosidase inhibitors and amylin), (3) immunotherapeutic agents, (4) incretin-based therapies, (5) recombinant human insulin-like growth factors, and (6) other promising therapeutics.	Biguanides	130-140	insulin	Homo sapiens	25-32
21840335-25	2011	Promising candidates are those that intersect with the critical signaling pathways identified above and include biguanides such as metformin that target the insulin signaling pathway, stilbenes (e.g. resveratrol) that affect sirtuin activity and drugs such as rapamycin that interact with mTOR signaling.	Biguanides	112-122	mechanistic target of rapamycin kinase	Homo sapiens	289-293
21282369-2	2011	We assess here the effects of the biguanide, metformin, on the expression of HIF-1alpha in diabetic nephropathy using renal proximal tubular cells and type 2 diabetic rats.	Biguanides	34-43	hypoxia inducible factor 1 subunit alpha	Rattus norvegicus	77-87
21386129-2	2011	Antidiabetic biguanides such as metformin decrease glucose, insulin and IGF-1 level.	Biguanides	13-23	insulin-like growth factor 1	Mus musculus	72-77
21329808-7	2011	Indeed, we found several bioactive drugs, such as pyrvinium pamoate, valinomycin, and rottlerin, that selectively suppressed 2DG-induced GRP78 promoter activity as versipelostatin and biguanide did.	Biguanides	184-193	heat shock protein family A (Hsp70) member 5	Homo sapiens	137-142
21765869-7	2011	Insulin sensitizers such as the thiazolidinediones, biguanides, glucagon-like peptide-1 receptor agonists, and the dipeptidyl peptidase IV inhibitors, also known as incretins, will be discussed with respect to their mechanism of action and how these drugs might target aspects of NASH pathophysiology.	Biguanides	52-62	insulin	Homo sapiens	0-7
22235508-7	2011	In the biguanide group the serum glucose status (abnormal fasting and non-fasting sugar and insulin levels and percentage of hyperinsulinemic cases) and menstrual abnormalities improved significantly after treatment (p < 0.05).	Biguanides	7-16	insulin	Homo sapiens	92-99
22235508-9	2011	Comparing the two groups, the improvements in fasting blood sugar and serum insulin levels were significantly better in the biguanide group (p = 0.04 for both parameters); whereas the improvements in serum total cholesterol (p < 0.001), low density lipoprotein (p < 0.001), CRP (p < 0.001) and acne status (p = 0.04) were significantly superior in the statin receivers.	Biguanides	124-133	insulin	Homo sapiens	76-83
29699342-8	2010	For improvement of anovulation because of hyperinsulinemia, insulin-sensitizing agents (biguanide and thiazolidinedione derivatives) are useful.	Biguanides	88-97	insulin	Homo sapiens	47-54
21098287-0	2010	Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling.	Biguanides	0-9	microtubule associated protein tau	Homo sapiens	28-31
21098287-0	2010	Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling.	Biguanides	0-9	mechanistic target of rapamycin kinase	Homo sapiens	52-56
21098287-0	2010	Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling.	Biguanides	0-9	protein phosphatase 2 catalytic subunit alpha	Homo sapiens	81-85
21189532-4	2010	Janumet is a fixed-dose combination of sitagliptin, a specific inhibitor of dipeptidylpeptidase-4 that blocks the rapid degradation of so-called incretin hormones (resulting in a potentiation of insulin secretion and reduction of glucagon secretion in a glucose-dependent manner), and of metformin, a biguanide compound that reduces glucose hepatic production and slightly improves insulin sensitivity.	Biguanides	301-310	dipeptidyl peptidase 4	Homo sapiens	76-97
20810672-2	2010	The biguanide metformin, which is widely prescribed for the treatment of type II diabetes, might be a good candidate for lung cancer chemoprevention because it activates AMP-activated protein kinase (AMPK), which can inhibit the mTOR pathway.	Biguanides	4-13	mechanistic target of rapamycin kinase	Mus musculus	229-233
20444419-3	2010	It is thought that agents that increase the cellular AMP/ATP ratio, such as the antidiabetic biguanides metformin and phenformin, inhibit mTORC1 through AMPK activation of TSC1/2-dependent or -independent mechanisms.	Biguanides	93-103	CREB regulated transcription coactivator 1	Mus musculus	138-144
20206412-4	2010	Insulin resistance can be treated through diet, physical exercise and the use of insulin-sensitizing agents such as biguanides or glitazones.	Biguanides	116-126	insulin	Homo sapiens	0-7
20206412-4	2010	Insulin resistance can be treated through diet, physical exercise and the use of insulin-sensitizing agents such as biguanides or glitazones.	Biguanides	116-126	insulin	Homo sapiens	81-88
20547605-1	2010	Metformin is a biguanide, insulin sensitiser that reduces blood sugar levels.	Biguanides	15-24	insulin	Homo sapiens	26-33
20444419-3	2010	It is thought that agents that increase the cellular AMP/ATP ratio, such as the antidiabetic biguanides metformin and phenformin, inhibit mTORC1 through AMPK activation of TSC1/2-dependent or -independent mechanisms.	Biguanides	93-103	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	153-157
20444419-3	2010	It is thought that agents that increase the cellular AMP/ATP ratio, such as the antidiabetic biguanides metformin and phenformin, inhibit mTORC1 through AMPK activation of TSC1/2-dependent or -independent mechanisms.	Biguanides	93-103	TSC complex subunit 1	Homo sapiens	172-176
20444419-4	2010	Unexpectedly, we found that biguanides inhibit mTORC1 signaling, not only in the absence of TSC1/2 but also in the absence of AMPK.	Biguanides	28-38	CREB regulated transcription coactivator 1	Mus musculus	47-53
20444419-4	2010	Unexpectedly, we found that biguanides inhibit mTORC1 signaling, not only in the absence of TSC1/2 but also in the absence of AMPK.	Biguanides	28-38	TSC complex subunit 1	Homo sapiens	92-98
20444419-6	2010	We found that the ability of biguanides to inhibit mTORC1 activation and signaling is, instead, dependent on the Rag GTPases.	Biguanides	29-39	CREB regulated transcription coactivator 1	Mus musculus	51-57
19564648-1	2010	Metformin is a biguanide, insulin sensitiser that reduces blood sugar levels.	Biguanides	15-24	insulin	Homo sapiens	26-33
20231400-0	2010	Persistent interactions between biguanide-based compound NB325 and CXCR4 result in prolonged inhibition of human immunodeficiency virus type 1 infection.	Biguanides	32-41	C-X-C motif chemokine receptor 4	Homo sapiens	67-72
20231400-1	2010	We previously demonstrated that the biguanide-based compound NB325 inhibits human immunodeficiency virus type 1 (HIV-1) infection by interacting with the CXCR4 viral coreceptor.	Biguanides	36-45	C-X-C motif chemokine receptor 4	Homo sapiens	154-159
20446599-2	2010	Thiazolidinedione (TZD) and biguanide counter insulin resistance, but act by different mechanisms.	Biguanides	28-37	insulin	Homo sapiens	46-53
20460925-4	2010	Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones.	Biguanides	121-131	insulin	Homo sapiens	0-7
20460925-4	2010	Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones.	Biguanides	121-131	insulin	Homo sapiens	95-102
19574203-6	2009	The unexpected ability of the anti-type II diabetes drug metformin to inactivate mTOR and decrease p70S6K1 activity further reveals that this biguanide, generally considered non-toxic and remarkably inexpensive, might be considered for new combinatorial lapatinib-based protocols in HER2-overexpressing breast cancer patients.	Biguanides	142-151	mechanistic target of rapamycin kinase	Homo sapiens	81-85
20095972-9	2009	Structural and catalytic similarities between LSD1 and polyamine oxidases facilitated the identification of biguanide, bisguanidine and oligoamine polyamine analogues that are potent inhibitors of LSD1.	Biguanides	108-117	lysine demethylase 1A	Homo sapiens	46-50
20095972-9	2009	Structural and catalytic similarities between LSD1 and polyamine oxidases facilitated the identification of biguanide, bisguanidine and oligoamine polyamine analogues that are potent inhibitors of LSD1.	Biguanides	108-117	lysine demethylase 1A	Homo sapiens	197-201
19768675-1	2009	Metformin, a biguanide that has been used to treat type 2 diabetes mellitus, is reportedly transported into human hepatocytes by human organic cation transporter 1 (hOCT1).	Biguanides	13-22	solute carrier family 22 member 1	Homo sapiens	135-163
19768675-1	2009	Metformin, a biguanide that has been used to treat type 2 diabetes mellitus, is reportedly transported into human hepatocytes by human organic cation transporter 1 (hOCT1).	Biguanides	13-22	solute carrier family 22 member 1	Homo sapiens	165-170
19768675-5	2009	Both biguanides proved to be good substrates for hOCT1.	Biguanides	5-15	solute carrier family 22 member 1	Homo sapiens	49-54
19768675-7	2009	Both biguanides were transported actively by hOCT1, with the active transport components much greater than passive transport components in both cases, suggesting that functional changes in hOCT1 might affect the transport of both compounds to the same degree.	Biguanides	5-15	solute carrier family 22 member 1	Homo sapiens	45-50
19768675-7	2009	Both biguanides were transported actively by hOCT1, with the active transport components much greater than passive transport components in both cases, suggesting that functional changes in hOCT1 might affect the transport of both compounds to the same degree.	Biguanides	5-15	solute carrier family 22 member 1	Homo sapiens	189-194
18768334-5	2009	In general, alpha-glucosidase inhibitors delay carbohydrate absorption, metiglinides and sulfonylureas increase insulin supply, and biguanides and thiazolidinediones enhance insulin action.	Biguanides	132-142	insulin	Homo sapiens	174-181
20122053-0	2010	Biguanide, but not thiazolidinedione, improved insulin resistance in Werner syndrome.	Biguanides	0-9	insulin	Homo sapiens	47-54
19807652-4	2009	Insulin sensitizers such as biguanides or AMP-activated protein kinase activator, but not glitazones, afforded cytoprotection through preventing (Deltapsi(m) collapse and activation of caspase-9 that was independent of cellular GSH.	Biguanides	28-38	insulin	Homo sapiens	0-7
19807652-4	2009	Insulin sensitizers such as biguanides or AMP-activated protein kinase activator, but not glitazones, afforded cytoprotection through preventing (Deltapsi(m) collapse and activation of caspase-9 that was independent of cellular GSH.	Biguanides	28-38	caspase 9	Homo sapiens	185-194
19761366-1	2009	AIMS: Antimalarial biguanides are metabolized by CYP2C19, thus genetic variation at the CYP2C locus might affect pharmacokinetics and so treatment outcome for malaria.	Biguanides	19-29	cytochrome P450 family 2 subfamily C member 19	Homo sapiens	49-56
19761366-7	2009	CONCLUSION: CYP2C19*17 determines antimalarial biguanide metabolic profile at the CYP2C19/CYP2C9 locus.	Biguanides	47-56	cytochrome P450 family 2 subfamily C member 19	Homo sapiens	12-19
19761366-7	2009	CONCLUSION: CYP2C19*17 determines antimalarial biguanide metabolic profile at the CYP2C19/CYP2C9 locus.	Biguanides	47-56	cytochrome P450 family 2 subfamily C member 19	Homo sapiens	82-89
19761366-7	2009	CONCLUSION: CYP2C19*17 determines antimalarial biguanide metabolic profile at the CYP2C19/CYP2C9 locus.	Biguanides	47-56	cytochrome P450 family 2 subfamily C member 9	Homo sapiens	90-96
19574203-6	2009	The unexpected ability of the anti-type II diabetes drug metformin to inactivate mTOR and decrease p70S6K1 activity further reveals that this biguanide, generally considered non-toxic and remarkably inexpensive, might be considered for new combinatorial lapatinib-based protocols in HER2-overexpressing breast cancer patients.	Biguanides	142-151	erb-b2 receptor tyrosine kinase 2	Homo sapiens	283-287
19146480-9	2009	Surprisingly, the structural analysis revealed that these novel, biguanide compounds do indeed bind at the active site of DHFR and additionally revealed the molecular basis by which they overcome drug resistance.	Biguanides	65-74	dihydrofolate reductase	Homo sapiens	122-126
19047650-0	2009	Specific interactions between the viral coreceptor CXCR4 and the biguanide-based compound NB325 mediate inhibition of human immunodeficiency virus type 1 infection.	Biguanides	65-74	C-X-C motif chemokine receptor 4	Homo sapiens	51-56
19047650-7	2009	Collectively, these results demonstrate that the biguanide-based compound NB325 inhibits HIV-1 infection by specifically interacting with the HIV-1 coreceptor CXCR4.	Biguanides	49-58	C-X-C motif chemokine receptor 4	Homo sapiens	159-164
17563269-7	2007	Biguanides and thiazolidinediones (TZDs) are two unique classes of oral antidiabetic agents that are the most commonly used medications to improve insulin sensitivity.	Biguanides	0-10	insulin	Homo sapiens	147-154
18801732-12	2008	Reduced CREB phosphorylation (Ser-129) associated with inactivation of GSK3beta by Ser-9 phosphorylation may be the major mechanism underlying PEPCK-C gene suppression by AMPK-activating agents such as biguanide.	Biguanides	202-211	cAMP responsive element binding protein 1	Homo sapiens	8-12
18801732-12	2008	Reduced CREB phosphorylation (Ser-129) associated with inactivation of GSK3beta by Ser-9 phosphorylation may be the major mechanism underlying PEPCK-C gene suppression by AMPK-activating agents such as biguanide.	Biguanides	202-211	glycogen synthase kinase 3 beta	Homo sapiens	71-79
18801732-12	2008	Reduced CREB phosphorylation (Ser-129) associated with inactivation of GSK3beta by Ser-9 phosphorylation may be the major mechanism underlying PEPCK-C gene suppression by AMPK-activating agents such as biguanide.	Biguanides	202-211	phosphoenolpyruvate carboxykinase 1	Homo sapiens	143-150
18801732-12	2008	Reduced CREB phosphorylation (Ser-129) associated with inactivation of GSK3beta by Ser-9 phosphorylation may be the major mechanism underlying PEPCK-C gene suppression by AMPK-activating agents such as biguanide.	Biguanides	202-211	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	171-175
18001251-9	2007	CONCLUSIONS: Our study showed that BIAsp 30 treatment safely improved glucose and lipid control in insulin-naive patients with Type 2 diabetes poorly controlled on BI plus SU/MEG and SU-only.	Biguanides	35-37	protein tyrosine phosphatase non-receptor type 4	Homo sapiens	175-178
19073504-3	2008	Metformin, a biguanide derivative used in the treatment of diabetes, reduces insulin levels in subjects with type 2 diabetes and other insulin-resistant states.	Biguanides	13-22	insulin	Homo sapiens	77-84
19073504-3	2008	Metformin, a biguanide derivative used in the treatment of diabetes, reduces insulin levels in subjects with type 2 diabetes and other insulin-resistant states.	Biguanides	13-22	insulin	Homo sapiens	135-142
17825080-6	2008	The pharmacological tools available to improve insulin sensitivity include the biguanides (metformin) and thiazolidinediones (rosiglitazone and pioglitazone).	Biguanides	79-89	insulin	Homo sapiens	47-54
18719601-8	2008	Two existing classes of antidiabetic drugs, that is, biguanides (for example, metformin) and the thiazolidinediones (for example, rosiglitazone), both act (at least in part) by activation of AMPK.	Biguanides	53-63	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	191-195
24692813-3	2008	Biguanides, such as metformin, and thiazolidinediones (TZDs), such as pioglitazone, improve insulin resistance.	Biguanides	0-10	insulin	Homo sapiens	92-99
17997341-11	2007	Moreover, the AMPK system is one of the probable targets for the anti-diabetic drugs biguanides and thiazolidinediones.	Biguanides	85-95	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	14-18
17717055-5	2007	Furthermore, the daily oral and intracerebroventricular treatment with biguanide antidiabetic drug metformin also induced AMPK phosphorylation in the central nervous system and increased food intake and life span in anorexic TB rats.	Biguanides	71-80	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	122-126
16988011-2	2006	In this study, we showed in primary human hepatocytes that: 1) 5"-phosphoribosyl-5-aminoimidazol-4-carboxamide 1-beta-d-ribofuranoside and the biguanide metformin, known activators of AMPK, dose-dependently increase the expression of CYP2B6 and CYP3A4 to an extent similar to that of PB.	Biguanides	143-152	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	234-240
17463086-5	2007	We now report that novel biguanide and bisguanidine polyamine analogues are potent inhibitors of LSD1.	Biguanides	25-34	lysine demethylase 1A	Homo sapiens	97-101
17339833-0	2007	Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer.	Biguanides	29-38	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	47-51
17339833-9	2007	This resulted in reduced phosphorylation of AMPK, establishing a link between biguanide-induced mitochondrial inhibition and AMPK activation.	Biguanides	78-87	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	44-48
17339833-9	2007	This resulted in reduced phosphorylation of AMPK, establishing a link between biguanide-induced mitochondrial inhibition and AMPK activation.	Biguanides	78-87	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	125-129
17705797-6	2007	Moreover, the potential importance of AMPK in metabolic diseases is supported by the notion that AMPK mediates the anti-diabetic action of biguanides and thiazolidinediones and that it might be involved in the metabolic syndrome.	Biguanides	139-149	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	38-42
17705797-6	2007	Moreover, the potential importance of AMPK in metabolic diseases is supported by the notion that AMPK mediates the anti-diabetic action of biguanides and thiazolidinediones and that it might be involved in the metabolic syndrome.	Biguanides	139-149	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	97-101
17476355-6	2007	make significant progress by integrating diverse data supporting the hypothesis that genetic variation in organic cation transporter 1 (OCT1) affects the response to the widely used biguanide metformin (see the related article beginning on page 1422).	Biguanides	182-191	solute carrier family 22 member 1	Homo sapiens	106-134
17476355-6	2007	make significant progress by integrating diverse data supporting the hypothesis that genetic variation in organic cation transporter 1 (OCT1) affects the response to the widely used biguanide metformin (see the related article beginning on page 1422).	Biguanides	182-191	solute carrier family 22 member 1	Homo sapiens	136-140
18613325-2	2007	It is a biguanide that decreases blood glucose concentration by mechanisms different from those of insulin secretagogues, such as sulphonylureas, or exogenous insulin therapy.	Biguanides	8-17	insulin	Homo sapiens	159-166
17969380-6	2007	Biguanides and thiazolidinediones (TZDs) are two classes of oral agents for the management of DM2 that improve insulin resistance, and thus have potential cardiovascular benefits beyond glycemic control alone.	Biguanides	0-10	immunoglobulin heavy diversity 1-14 (non-functional)	Homo sapiens	94-97
17969380-6	2007	Biguanides and thiazolidinediones (TZDs) are two classes of oral agents for the management of DM2 that improve insulin resistance, and thus have potential cardiovascular benefits beyond glycemic control alone.	Biguanides	0-10	insulin	Homo sapiens	111-118
16988011-2	2006	In this study, we showed in primary human hepatocytes that: 1) 5"-phosphoribosyl-5-aminoimidazol-4-carboxamide 1-beta-d-ribofuranoside and the biguanide metformin, known activators of AMPK, dose-dependently increase the expression of CYP2B6 and CYP3A4 to an extent similar to that of PB.	Biguanides	143-152	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	245-251
17087301-5	2006	For patients with insulin resistance, biguanide or thiazolidinediones are the drugs of choice.	Biguanides	38-47	insulin	Homo sapiens	18-25
17075781-0	2006	Biguanides enhance glucose utilization and insulin action in peripheral tissues: an old finding from the sixties of the last century.	Biguanides	0-10	insulin	Homo sapiens	43-50
16901933-1	2006	In patients with type 2 non-insulin-dependent diabetes mellitus (NIDDM), the biguanide, metformin, exerts its antihyperglycemic effect by improving insulin sensitivity, which is associated with decreased level of circulating free fatty acids (FFA).	Biguanides	77-86	insulin	Homo sapiens	28-35
16489105-4	2006	In this work, we studied the relationship between AMPK activation and glucose uptake stimulation by biguanides and oligomycin, another AMPK activator, in both insulin-sensitive and insulin-resistant cardiomyocytes.	Biguanides	100-110	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	50-54
16489105-10	2006	We concluded that AMPK activators, like biguanides and oligomycin, are able to restore glucose uptake stimulation, in the absence of insulin, in insulin-resistant cardiomyocytes via the additive activation of AMPK and PKB.	Biguanides	40-50	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	18-22
16489105-10	2006	We concluded that AMPK activators, like biguanides and oligomycin, are able to restore glucose uptake stimulation, in the absence of insulin, in insulin-resistant cardiomyocytes via the additive activation of AMPK and PKB.	Biguanides	40-50	insulin	Homo sapiens	145-152
16489105-10	2006	We concluded that AMPK activators, like biguanides and oligomycin, are able to restore glucose uptake stimulation, in the absence of insulin, in insulin-resistant cardiomyocytes via the additive activation of AMPK and PKB.	Biguanides	40-50	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	209-213
16489105-10	2006	We concluded that AMPK activators, like biguanides and oligomycin, are able to restore glucose uptake stimulation, in the absence of insulin, in insulin-resistant cardiomyocytes via the additive activation of AMPK and PKB.	Biguanides	40-50	protein tyrosine kinase 2 beta	Homo sapiens	218-221
16489105-5	2006	In insulin-sensitive cardiomyocytes, insulin, biguanides and oligomycin were able to stimulate glucose uptake with the same efficiency.	Biguanides	46-56	insulin	Homo sapiens	3-10
16489105-6	2006	Stimulation of glucose uptake by insulin or biguanides was correlated to protein kinase B (PKB) or AMPK activation, respectively, and were additive.	Biguanides	44-54	protein tyrosine kinase 2 beta	Homo sapiens	73-89
16489105-6	2006	Stimulation of glucose uptake by insulin or biguanides was correlated to protein kinase B (PKB) or AMPK activation, respectively, and were additive.	Biguanides	44-54	protein tyrosine kinase 2 beta	Homo sapiens	91-94
16489105-6	2006	Stimulation of glucose uptake by insulin or biguanides was correlated to protein kinase B (PKB) or AMPK activation, respectively, and were additive.	Biguanides	44-54	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	99-103
16489105-7	2006	In insulin-resistant cardiomyocytes, where insulin stimulation of glucose uptake was greatly reduced, biguanides or oligomycin, in the absence of insulin, induced a higher stimulation of glucose uptake than that obtained in insulin-sensitive cells.	Biguanides	102-112	insulin	Homo sapiens	3-10
15798962-10	2005	The improvement in liver function parameters known to be associated with fatty liver in the present study, together with an improvement in fatty liver reported for another class of insulin sensitizers, biguanides, suggests that thiazolidinediones may have a beneficial effect on fatty liver.	Biguanides	202-212	insulin	Homo sapiens	181-188
16768125-5	2006	The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver.	Biguanides	42-52	insulin	Homo sapiens	4-11
16768125-5	2006	The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver.	Biguanides	42-52	insulin	Homo sapiens	139-146
16231594-7	2005	Two classes of drugs have been shown to correct insulin resistance: biguanides (e.g., metformin) and thiazolidinediones (e.g., rosiglitazone and pioglitazone).	Biguanides	68-78	insulin	Homo sapiens	48-55
16817087-2	2006	The biguanide metformin has encouraging effects on several metabolic aspects of the syndrome, including insulin sensitivity, plasma glucose concentration and lipid profile.	Biguanides	4-13	insulin	Homo sapiens	104-111
16914073-3	2006	Two key classes of insulin-sensitizing agents--the biguanides (principally metformin) and thiazolidinediones (pioglitazone and rosiglitazone)--have distinct molecular mechanisms of action and differing effects on metabolic dysfunction.	Biguanides	51-61	insulin	Homo sapiens	19-26
17144168-4	2006	Insulin-sensitizing adipokines (leptin and adiponectin) and anti-diabetic drugs (thiazolidinediones and biguanides) are acting in part through the activation of AMPK.	Biguanides	104-114	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	161-165
16219007-1	2005	The biguanide, metformin, sensitizes the liver to the effect of insulin, suppressing hepatic glucose output.	Biguanides	4-13	insulin	Homo sapiens	64-71
15919715-6	2005	The biguanide phenformin has been shown to independently decrease ion transport processes, influence cellular metabolism and activate AMPK.	Biguanides	4-13	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	134-138
15044053-2	2004	In this report, we show that biguanides promote GLP-2 release.	Biguanides	29-39	glucagon-like peptide 2 receptor	Mus musculus	48-53
17877135-7	2005	According to several surveys the drugs reducing insulin resistance, such as biguanides or thiazolidinediones, as well as those improving lipid disorders (fibrates) seem to be efficient, but it needs to be confirmed in randomized clinical trials.	Biguanides	76-86	insulin	Homo sapiens	48-55
16372821-15	2005	The biguanide metformin is not significantly metabolised but polymorphisms in the organic cation transporter (OCT) 1 and OCT2 may determine its pharmacokinetic variability.	Biguanides	4-13	solute carrier family 22 member 1	Homo sapiens	82-116
16372821-15	2005	The biguanide metformin is not significantly metabolised but polymorphisms in the organic cation transporter (OCT) 1 and OCT2 may determine its pharmacokinetic variability.	Biguanides	4-13	POU class 2 homeobox 2	Homo sapiens	121-125
16053338-2	2005	Biguanides and thiazolidinediones are the two currently available classes of anti-hyperglycemic agents with insulin-sensitizing properties.	Biguanides	0-10	insulin	Homo sapiens	108-115
15206158-2	2004	Oral hypoglycemic agents such as thiazolidinediones and biguanides improve glycemic control by reducing insulin resistance.	Biguanides	56-66	insulin	Homo sapiens	104-111
15783073-7	2005	The order of the potencies of unlabeled biguanides to inhibit [14C]metformin transport by hOCT2 was phenformin > buformin > metformin.	Biguanides	40-50	solute carrier family 22 member 2	Homo sapiens	90-95
15529521-2	2004	Metformin (a biguanide) and rosiglitazone (a thiazolidinedione) counter insulin resistance, acting by different cellular mechanisms.	Biguanides	13-22	insulin	Homo sapiens	72-79
15039452-2	2004	We previously found that the biguanide metformin, an antidiabetic agent, causes a significant increase of plasma active GLP-1 level in the presence of dipeptidyl peptidase IV (DPPIV) inhibitor in normal rats.	Biguanides	29-38	glucagon	Rattus norvegicus	120-125
15039452-2	2004	We previously found that the biguanide metformin, an antidiabetic agent, causes a significant increase of plasma active GLP-1 level in the presence of dipeptidyl peptidase IV (DPPIV) inhibitor in normal rats.	Biguanides	29-38	dipeptidylpeptidase 4	Rattus norvegicus	151-174
15039452-2	2004	We previously found that the biguanide metformin, an antidiabetic agent, causes a significant increase of plasma active GLP-1 level in the presence of dipeptidyl peptidase IV (DPPIV) inhibitor in normal rats.	Biguanides	29-38	dipeptidylpeptidase 4	Rattus norvegicus	176-181
15044053-9	2004	These results suggest that GLP-2 is co-secreted with GLP-1 flollowing biguanide stimulation, and that the combination of metformin with a DPPIV inhibitor might a useful oral treatment for gastrointestinal damage, based on GLP-2 actions.	Biguanides	70-79	glucagon	Mus musculus	53-58
12946541-13	2003	The combination of a thiazolidinedione and a biguanide reduces hyperglycemia, hyperinsulinemia, and insulin resistance and improves factors that have been implicated in the pathogenesis of cardiovascular complications.	Biguanides	45-54	insulin	Homo sapiens	83-90
15209435-21	2004	Metformin, a biguanide oral antidiabetic agent, was shown to affect insulin resistance by decreasing enzymatic activity of overexpressed PC-1 molecules in obese type 2 diabetics.	Biguanides	13-22	insulin	Homo sapiens	68-75
15209435-21	2004	Metformin, a biguanide oral antidiabetic agent, was shown to affect insulin resistance by decreasing enzymatic activity of overexpressed PC-1 molecules in obese type 2 diabetics.	Biguanides	13-22	ectonucleotide pyrophosphatase/phosphodiesterase 1	Homo sapiens	137-141
14502100-4	2003	Metformin is a biguanide compound which is antihyperglycaemic, reduces insulin resistance and has cardioprotective effects on lipids, thrombosis and blood flow.	Biguanides	15-24	insulin	Homo sapiens	71-78
12906931-3	2003	Here, various biguanide derivatives are reported to be metal-interactive inhibitors of cathepsin B from mammals and falcipain-2 from Plasmodium falciparum.	Biguanides	14-23	cathepsin B	Homo sapiens	87-98
14760321-7	2004	Hypoglycemic therapy including only insulin and/or sulfonylurea (insulin-providing; n = 1473) was associated with higher 90-day death/MI/SRI compared with therapy that included only biguanide and/or thiazolidinedione therapy (insulin-sensitizing; n = 100) (12.0% vs 5.0%); (adjusted OR, 2.1 [1.2, 3.7]).	Biguanides	182-191	insulin	Homo sapiens	65-72
14760321-7	2004	Hypoglycemic therapy including only insulin and/or sulfonylurea (insulin-providing; n = 1473) was associated with higher 90-day death/MI/SRI compared with therapy that included only biguanide and/or thiazolidinedione therapy (insulin-sensitizing; n = 100) (12.0% vs 5.0%); (adjusted OR, 2.1 [1.2, 3.7]).	Biguanides	182-191	insulin	Homo sapiens	65-72
12946541-17	2003	For example, the combination of a thiazolidinedione and a biguanide improves insulin sensitivity and lowers blood glucose through complementary pathways, and therefore produces an additive effect.	Biguanides	58-67	insulin	Homo sapiens	77-84
12644585-2	2003	We reported previously that biguanides are good substrates of rat organic cation transporter 1 (Oct1; Slc22a1) and, using Oct1(-/-) mice, that mouse Oct1 is responsible for the hepatic uptake of a biguanide, metformin.	Biguanides	28-38	solute carrier family 22 member 1	Rattus norvegicus	66-94
12785129-8	2003	The combination of a TZD and a biguanide, which improves insulin sensitivity and lowers blood glucose through different pathways, offers significant benefits and may help prevent or delay prevent complications associated with type 2 diabetes.	Biguanides	31-40	insulin	Homo sapiens	57-64
12644585-2	2003	We reported previously that biguanides are good substrates of rat organic cation transporter 1 (Oct1; Slc22a1) and, using Oct1(-/-) mice, that mouse Oct1 is responsible for the hepatic uptake of a biguanide, metformin.	Biguanides	28-38	solute carrier family 22 member 1	Rattus norvegicus	96-100
12644585-2	2003	We reported previously that biguanides are good substrates of rat organic cation transporter 1 (Oct1; Slc22a1) and, using Oct1(-/-) mice, that mouse Oct1 is responsible for the hepatic uptake of a biguanide, metformin.	Biguanides	28-38	solute carrier family 22 member 1	Rattus norvegicus	102-109
12644585-2	2003	We reported previously that biguanides are good substrates of rat organic cation transporter 1 (Oct1; Slc22a1) and, using Oct1(-/-) mice, that mouse Oct1 is responsible for the hepatic uptake of a biguanide, metformin.	Biguanides	28-37	solute carrier family 22 member 1	Rattus norvegicus	66-94
12644585-2	2003	We reported previously that biguanides are good substrates of rat organic cation transporter 1 (Oct1; Slc22a1) and, using Oct1(-/-) mice, that mouse Oct1 is responsible for the hepatic uptake of a biguanide, metformin.	Biguanides	28-37	solute carrier family 22 member 1	Rattus norvegicus	96-100
12644585-2	2003	We reported previously that biguanides are good substrates of rat organic cation transporter 1 (Oct1; Slc22a1) and, using Oct1(-/-) mice, that mouse Oct1 is responsible for the hepatic uptake of a biguanide, metformin.	Biguanides	28-37	solute carrier family 22 member 1	Rattus norvegicus	102-109
12469622-8	2002	CONCLUSION: Biguanide derivatives are a perspective group of drugs for treatment of the diseases running with insulin resistance.	Biguanides	12-21	insulin	Homo sapiens	110-117
12130709-4	2002	Buformin and phenformin, two other biguanides, were also transported by rOct1 with a higher affinity than metformin: their K(m) values were 49 and 16 microM, respectively.	Biguanides	35-45	solute carrier family 22 member 1	Rattus norvegicus	72-77
12240953-0	2002	Interactions of n-tetraalkylammonium compounds and biguanides with a human renal organic cation transporter (hOCT2).	Biguanides	51-61	POU class 2 homeobox 2	Homo sapiens	109-114
12669266-1	2003	Biguanides and thiazolidinediones (TZDs), which are primarily used as anti-diabetic drugs, are also associated with other beneficial effects on cardiovascular risk factors such as reduced plasma plasminogen activator inhibitor-1 (PAI-1) concentration in both diabetic and non-diabetic obese subjects.	Biguanides	0-10	serpin family E member 1	Homo sapiens	195-228
12669266-1	2003	Biguanides and thiazolidinediones (TZDs), which are primarily used as anti-diabetic drugs, are also associated with other beneficial effects on cardiovascular risk factors such as reduced plasma plasminogen activator inhibitor-1 (PAI-1) concentration in both diabetic and non-diabetic obese subjects.	Biguanides	0-10	serpin family E member 1	Homo sapiens	230-235
12526635-4	2002	For those with type 2 diabetes, treatment with insulin-sensitizing drugs, such as the TZDs and biguanides, can improve glycemic control and prevent some of the adverse consequences of the disease.	Biguanides	95-105	insulin	Homo sapiens	47-54
11712411-2	2001	Recently, either biguanides or thiazolidinediones among oral hypoglycemic agents is widely used to patients with type 2 diabetes mellitus for reversal of insulin resistance.	Biguanides	17-27	insulin	Homo sapiens	154-161
11712411-3	2001	As clinical difference between biguanides and thiazolidinediones in reducing blood glucose, the former primarily lowers endogenous glucose production presumably at the level of liver, whereas the latter increases insulin-mediated peripheral glucose disposal, which occurs predominantly in skeletal muscle.	Biguanides	31-41	insulin	Homo sapiens	213-220
10929918-3	2000	Metformin is a biguanide antihyperglycemic agent that increases peripheral insulin sensitivity, reduces hepatic gluconeogenesis, and decreases intestinal glucose absorption.	Biguanides	15-24	insulin	Homo sapiens	75-82
11460576-0	2001	Metformin, the rebirth of a biguanide: mechanism of action and place in the prevention and treatment of insulin resistance.	Biguanides	28-37	insulin	Homo sapiens	104-111
10929931-11	2000	The third modality consists of agents such as biguanides and thiazolidinediones which enhance insulin sensitivity, or agents that decrease insulin requirements like the alpha-glucosidase inhibitors.	Biguanides	46-56	insulin	Homo sapiens	94-101
12622887-6	2001	The association biguanides and S, in particular glibenclamide plus metformin, is now widely used by diabetologists in SF since glibenclamide improves insulin secretion while metformin exerts its antidiabetic.	Biguanides	16-26	insulin	Homo sapiens	150-157
10872292-7	2000	The group of insulin sensitizers includes the biguanide, metformin and the thiazolidinediones or glitazones (rosiglitazone, pioglitazone).	Biguanides	46-55	insulin	Homo sapiens	13-20
10480188-4	1999	The treatment of insulin resistance was for a long time limited to dietary and exercise programmes, a biguanide, metformine, and benfluorex, a phenylethylamine derivative; the mechanisms of action of both drugs are now better understood and their indications more precisely targeted.	Biguanides	102-111	insulin	Homo sapiens	17-24
10701409-11	2000	Rapid-release analogs and alpha-glucosidase inhibitors appear to be promising; biguanides affect insulin resistance.	Biguanides	79-89	insulin	Homo sapiens	97-104
10337452-1	1999	The purpose of the study was the comparison of the effect of the oral therapy of non-insulin-dependent diabetes mellitus (NIDDM) with either a sulphonylurea or biguanide derivative on plasma amylin level.	Biguanides	160-169	islet amyloid polypeptide	Homo sapiens	191-197
10643211-7	1999	The biguanides act by decreasing hepatic glucose production and by increasing peripheral insulin sensitivity.	Biguanides	4-14	insulin	Homo sapiens	89-96
9739502-8	1998	Thus, the use of alpha-glucosidase inhibitors should be considered: (i) as a first-choice treatment in newly diagnosed patients; (ii) in individuals whose DM is not well controlled with any other type of treatment; (iii) as an alternative to sulphonylureas or biguanides in patients at risk from hypoglycaemia or lactic acidosis, respectively.	Biguanides	260-270	sucrase-isomaltase	Homo sapiens	17-34
9824974-4	1998	The biguanide metformin is especially useful in obese, insulin-resistant patients.	Biguanides	4-13	insulin	Homo sapiens	55-62
9451469-10	1997	Activation of cyclic PIP synthetase by biguanides can also be demonstrated in intact cells.	Biguanides	39-49	prolactin induced protein	Rattus norvegicus	21-24
9715377-4	1998	Life style changes (exercise, weight reduction) and pharmacological agents (e.g., biguanides and thiazolidendiones) that reduce insulin resistance or increase insulin sensitivity clearly have major beneficial effects (122, 144-146, 153-155).	Biguanides	82-92	insulin	Homo sapiens	128-135
9134273-8	1997	Diet and exercise are central, and novel orally active hyperglycemic agents such as the biguanides and the thiazolidinediones that sensitize diverse tissues to insulin offer particular promise.	Biguanides	88-98	insulin	Homo sapiens	160-167
9609021-1	1997	BACKGROUND: Metformin is a biguanide often used in obese diabetics that improves tissue sensitivity to insulin.	Biguanides	27-36	insulin	Homo sapiens	103-110
9340472-10	1997	Biguanides, similarly to weight reduction, lead to a reduction of hyperinsulinaemia, which is by contrast exacerbated by sulfonylureas and, in particular, exogenous insulin.	Biguanides	0-10	insulin	Homo sapiens	71-78
8914439-5	1996	Metformin, an antihyperglycemic drug of the biguanide class, may be effective in subjects with IGT by reducing hepatic glucose output, enhancing insulin sensitivity, or through other mechanisms such as weight loss.	Biguanides	44-53	insulin	Homo sapiens	145-152
9209206-3	1997	Metformin, an oral biguanide, ameliorates hyperglycemia by improving peripheral sensitivity to insulin, and reducing gastrointestinal glucose absorption and hepatic glucose production.	Biguanides	19-28	insulin	Homo sapiens	95-102
8879966-7	1996	A group of 30 diabetic patients were treated for 3 months with metformin, an antidiabetic biguanide compound which has been reported to reduce PAI-1 levels both in diabetic and in non-diabetic patients.	Biguanides	90-99	serpin family E member 1	Homo sapiens	143-148
15251529-4	1996	The biguanide metformin has been shown to suppress hepatic glucose production, augment glucose uptake, and enhance insulin action in peripheral tissues.	Biguanides	4-13	insulin	Homo sapiens	115-122
8656173-1	1996	Metformin is a biguanide that can used alone or in combination with sulfonylureas or insulin in the treatment of non-insulin-dependent diabetes mellitus (NIDDM).	Biguanides	15-24	insulin	Homo sapiens	85-92
8656173-3	1996	Biguanides reduce hyperglycemia by increasing, insulin sensitivity, decreasing glucose absorption, and inhibiting hepatic gluconeogenesis.	Biguanides	0-10	insulin	Homo sapiens	47-54
7640152-0	1995	The role of S-mephenytoin hydroxylase (CYP2C19) in the metabolism of the antimalarial biguanides.	Biguanides	86-96	cytochrome P450 family 2 subfamily C member 19	Homo sapiens	39-46
7608255-2	1995	The present study was conducted to assess the effect of administration of the biguanide metformin, a drug commonly used in the treatment of diabetes mellitus, on androgen and insulin levels in 24 hirsute patients.	Biguanides	78-87	insulin	Homo sapiens	175-182
8187467-6	1994	Action of sulphonylureas are simulated by changing the insulin secretion rate of the beta-cell, biguanides enhance sensitivity of the peripheral tissue for insulin and Acarbose delays glucose absorption from the intestines.	Biguanides	96-106	insulin	Homo sapiens	55-62
7818725-1	1994	In a double-blind cross-over study, we investigated a possible influence of the alpha-glucosidase inhibitor acarbose on the bioavailability of the biguanide compound metformin.	Biguanides	147-156	sucrase-isomaltase	Homo sapiens	80-97
8126125-2	1994	This study was conducted to assess the influence of physiological concentrations of insulin on serum adrenal steroid levels by lowering circulating insulin in nondiabetic men through the administration of the biguanide metformin.	Biguanides	209-218	insulin	Homo sapiens	84-91
8126125-2	1994	This study was conducted to assess the influence of physiological concentrations of insulin on serum adrenal steroid levels by lowering circulating insulin in nondiabetic men through the administration of the biguanide metformin.	Biguanides	209-218	insulin	Homo sapiens	148-155
8187467-6	1994	Action of sulphonylureas are simulated by changing the insulin secretion rate of the beta-cell, biguanides enhance sensitivity of the peripheral tissue for insulin and Acarbose delays glucose absorption from the intestines.	Biguanides	96-106	insulin	Homo sapiens	156-163
7926420-10	1993	Biguanides like metformin have also been found to reduce insulin resistance.	Biguanides	0-10	insulin	Homo sapiens	57-64
8056129-8	1994	These findings offer further evidence that metabolic control is improved after biguanide addition to sulphonylurea treatment, and support the hypothesis that biguanides improve insulin sensitivity both at the hepatic and peripheral (muscular) levels, as well as triglyceride metabolism.	Biguanides	158-168	insulin	Homo sapiens	177-184
20668229-2	2010	We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity.	Biguanides	123-132	serine/threonine kinase 11	Homo sapiens	38-42
8475636-5	1993	The biguanide metformin is suitable to diminish peripheral insulin resistance, gluconeogenesis, and intestinal glucose absorption on cellular mechanisms others than betacytotropic effects.	Biguanides	4-13	insulin	Homo sapiens	59-66
1297607-0	1992	Effect of biguanides on insulin release from isolated pancreatic islets.	Biguanides	10-20	insulin	Homo sapiens	24-31
1505458-6	1992	The latter effect was additive to the maximum effect of metformin, suggesting that the biguanide stimulates hexose uptake into muscle cells by an insulin-independent mechanism.	Biguanides	87-96	insulin	Homo sapiens	146-153
2204978-8	1990	The action of biguanides on insulin sensitivity is confirmed.	Biguanides	14-24	insulin	Homo sapiens	28-35
1568370-3	1992	Therefore, the addition of biguanides in those patients, was able to reduce blood glucose levels and to improve insulin resistance.	Biguanides	27-37	insulin	Homo sapiens	112-119
1306517-6	1992	For instance, biguanides and thiazolidine-dione facilitate translocation to the membrane of glucose transporter in presence of insulin.	Biguanides	14-24	insulin	Homo sapiens	127-134
1834486-5	1991	Some studies have thus shown that insulin requirements were significantly decreased during the administration of biguanides, and effect which seemed to be maximal shortly after commencing the drug.	Biguanides	113-123	insulin	Homo sapiens	34-41
20668229-2	2010	We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity.	Biguanides	123-132	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	43-47
20668229-2	2010	We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity.	Biguanides	123-132	TSC complex subunit 1	Homo sapiens	48-51
20668229-2	2010	We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity.	Biguanides	123-132	mechanistic target of rapamycin kinase	Homo sapiens	191-220
20668229-2	2010	We show in our current study that the LKB1/AMPK/TSC tumor suppressor axis is functional in AML and can be activated by the biguanide molecule metformin, resulting in a specific inhibition of mammalian target of rapamycin (mTOR) catalytic activity.	Biguanides	123-132	mechanistic target of rapamycin kinase	Homo sapiens	222-226
34760762-10	2021	Among the antidiabetic drugs, most frequently prescribed was insulin and least prescribed was DPP-4 inhibitors and Biguanide+DPP-4 inhibitor both.	Biguanides	115-124	dipeptidyl peptidase 4	Homo sapiens	125-130
34771022-5	2021	The fewer differences in the RMW values of both biguanide derivatives were ensured by the RP-TLC system composed of RP2, RP18, and RP18W plates and the mixture composed of methanol, propan-1-ol, and acetonitrile as an organic modifier compared to the NP-TLC analysis.	Biguanides	48-57	RP2 activator of ARL3 GTPase	Homo sapiens	116-119
34771022-5	2021	The fewer differences in the RMW values of both biguanide derivatives were ensured by the RP-TLC system composed of RP2, RP18, and RP18W plates and the mixture composed of methanol, propan-1-ol, and acetonitrile as an organic modifier compared to the NP-TLC analysis.	Biguanides	48-57	pre-mRNA processing factor 3	Homo sapiens	121-125
34646263-12	2021	We observed that the antidiabetic biguanide metformin, a putative anti-inflammatory agent, also upregulates ACE2 expression in Calu-3 and endothelial cells.	Biguanides	34-43	angiotensin converting enzyme 2	Homo sapiens	108-112
34646376-1	2021	As a first-line treatment for diabetes, the insulin-sensitizing biguanide, metformin, regulates glucose levels and positively affects cardiovascular function in patients with diabetes and cardiovascular complications.	Biguanides	64-73	insulin	Homo sapiens	44-51
34794886-6	2021	We revealed that this biguanide (MET) opposes the LPS-induced dysregulation of the lung microvasculature, since it suppressed the formation of filamentous actin stress fibers, and deactivated cofilin.	Biguanides	22-31	SAFB like transcription modulator	Homo sapiens	33-36
34794886-6	2021	We revealed that this biguanide (MET) opposes the LPS-induced dysregulation of the lung microvasculature, since it suppressed the formation of filamentous actin stress fibers, and deactivated cofilin.	Biguanides	22-31	cofilin 1	Homo sapiens	192-199
34753372-3	2022	One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways.	Biguanides	63-72	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	175-205
34753372-3	2022	One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways.	Biguanides	63-72	protein kinase AMP-activated catalytic subunit alpha 2	Homo sapiens	207-211
34753372-3	2022	One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways.	Biguanides	63-72	mechanistic target of rapamycin kinase	Homo sapiens	231-260
34753372-3	2022	One of the medications widely used in the treatment of T2DM is biguanide derivative, metformin, which exerts promising anticancer properties principally through activation of adenosine monophosphate kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) pathways.	Biguanides	63-72	mechanistic target of rapamycin kinase	Homo sapiens	262-266
34481023-5	2021	The biguanide and ursodeoxycholic acid dual-modified multifunctional albumin was synthesized to enhance the anti-tumor effect and tumor target efficiency.	Biguanides	4-13	albumin	Homo sapiens	69-76
34239878-4	2021	In clinics, biguanides and thiazolidinediones are prescribed to patients with metabolic disorders through activating AMPK signaling and inhibiting complex I in the mitochondria, leading to a reduction in mitochondrial respiration and elevated ATP production.	Biguanides	12-22	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	117-121
34439897-2	2021	The biguanide seems to directly impair cancer energy asset, with the consequent phosphorylation of AMP-activated protein kinase (AMPK) inhibiting cell proliferation and tumor growth.	Biguanides	4-13	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	99-127
34439897-2	2021	The biguanide seems to directly impair cancer energy asset, with the consequent phosphorylation of AMP-activated protein kinase (AMPK) inhibiting cell proliferation and tumor growth.	Biguanides	4-13	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	129-133
34439169-9	2021	As currently available SHMT2 inhibitors have not yet reached the clinic, our current data establishing the structural and mechanistic bases of metformin as a small-molecule, PLP-competitive inhibitor of the SHMT2 activating oligomerization should benefit future discovery of biguanide skeleton-based novel SHMT2 inhibitors in cancer prevention and treatment.	Biguanides	275-284	glycine hydroxymethyltransferase SHM2	Saccharomyces cerevisiae S288C	306-311
34422646-1	2021	Objectives: Anti-diabetic biguanide drugs such as metformin may have anti-tumorigenic effects by behaving as AMPK activators and mTOR inhibitors.	Biguanides	26-35	protein kinase AMP-activated catalytic subunit alpha 1	Homo sapiens	109-113
34422646-1	2021	Objectives: Anti-diabetic biguanide drugs such as metformin may have anti-tumorigenic effects by behaving as AMPK activators and mTOR inhibitors.	Biguanides	26-35	mechanistic target of rapamycin kinase	Homo sapiens	129-133
34367462-8	2021	Cell proliferation and tumor growth were strongly inhibited by biguanide phenformin via targeting of mitochondrial OXPHOS complex 1 in EGFR-TKI-resistant NSCLC cells.	Biguanides	63-72	epidermal growth factor receptor	Homo sapiens	135-139
35015172-2	2022	We and others previously demonstrated that metformin reduced splenomegaly and platelets counts in peripheral blood in JAK2V617F pre-clinical MPN models, which highlighted the antineoplastic potential of biguanides for MPN treatment.	Biguanides	203-213	Janus kinase 2	Mus musculus	118-122
35454163-1	2022	Metformin is a synthetic biguanide that improves insulin sensitivity and reduces hepatic gluconeogenesis.	Biguanides	25-34	insulin	Homo sapiens	49-56
35135603-13	2022	In particular, the biguanide-based derivatives Q48 and Q54, represent the leads to develop novel compounds endowed with better pharmacological profiles than metformin, to act as CLIC1-blockers for the treatment of CLIC1-expressing glioblastomas, in a precision medicine approach.	Biguanides	19-28	chloride intracellular channel 1	Danio rerio	214-219
35142271-10	2022	RESULTS: The optimal biguanide derivatives 10a-10c, 11d exhibited IC50 values of 2.21-9.59microMu for five human cancer cell lines, significantly better than the control drug proguanil.	Biguanides	21-30	Rho GTPase activating protein 9	Homo sapiens	47-50
35135603-0	2022	Chloride intracellular channel 1 activity is not required for glioblastoma development but its inhibition dictates glioma stem cell responsivity to novel biguanide derivatives.	Biguanides	154-163	chloride intracellular channel 1	Danio rerio	0-32
35135603-13	2022	In particular, the biguanide-based derivatives Q48 and Q54, represent the leads to develop novel compounds endowed with better pharmacological profiles than metformin, to act as CLIC1-blockers for the treatment of CLIC1-expressing glioblastomas, in a precision medicine approach.	Biguanides	19-28	chloride intracellular channel 1	Danio rerio	178-183