PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
29104662-10	2017	Further analysis revealed that IL-15 expression was elevated following the administration of inhaled glucocorticosteroids (iGCs; P=0.024), and reduced following methylxanthine treatment (P<0.001).	methylxanthine	161-175	interleukin 15	Homo sapiens	31-36
29710033-0	2018	Methylxanthine Derivative-Rich Cacao Extract Suppresses Differentiation of Adipocytes through Downregulation of PPARgamma and C/EBPs.	methylxanthine	0-14	peroxisome proliferator activated receptor gamma	Mus musculus	112-121
25818199-0	2015	Methylxanthines Increase Expression of the Splicing Factor SRSF2 by Regulating Multiple Post-transcriptional Mechanisms.	methylxanthine	0-15	serine and arginine rich splicing factor 2	Homo sapiens	59-64
28212276-2	2017	Pentoxifylline (PTX), a methylxanthine derivative, has been reported to suppress the production of tumor necrosis factor (TNF)-alpha and possess anti-inflammatory properties.	methylxanthine	24-38	tumor necrosis factor	Mus musculus	99-132
27474406-3	2016	The aim of this study was to evaluate whether theophylline (used in asthma therapy) and two other methylxanthines (pentoxifylline and its active metabolite lisofylline), may affect transforming growth factor beta1-induced fibroblast to myofibroblast transition in bronchial fibroblasts derived from asthmatic patients.	methylxanthine	98-113	potassium calcium-activated channel subfamily M regulatory beta subunit 1	Homo sapiens	208-213
27474406-4	2016	We show here for the first time that selected methylxanthines effectively reduce transforming growth factor beta1-induced myofibroblast formation in asthmatic bronchial fibroblast populations.	methylxanthine	46-61	potassium calcium-activated channel subfamily M regulatory beta subunit 1	Homo sapiens	108-113
27458036-7	2016	XOR activity has a degradation function toward thiopurine nucleotides, pyrazinoic acid, methylxanthines and tolbutamide, whose half-life may be prolonged by the use of XOR inhibitors.	methylxanthine	88-103	xanthine dehydrogenase	Homo sapiens	0-3
27458036-7	2016	XOR activity has a degradation function toward thiopurine nucleotides, pyrazinoic acid, methylxanthines and tolbutamide, whose half-life may be prolonged by the use of XOR inhibitors.	methylxanthine	88-103	xanthine dehydrogenase	Homo sapiens	168-171
25818199-1	2015	We have previously reported that the methylxanthine caffeine increases expression of the splicing factor SRSF2, the levels of which are normally controlled by a negative autoregulatory loop.	methylxanthine	37-51	serine and arginine rich splicing factor 2	Homo sapiens	105-110
25386474-12	2014	CONCLUSION: This study reaffirms the rationale of use of Methylxanthines as add on therapy with LAMA in COPD management and cardiac safety level with Acebrophylline was considerable.	methylxanthine	57-72	COPD	Homo sapiens	104-108
24551237-0	2014	Synergistic effects of polyphenols and methylxanthines with Leucine on AMPK/Sirtuin-mediated metabolism in muscle cells and adipocytes.	methylxanthine	39-54	protein kinase AMP-activated non-catalytic subunit beta 1	Homo sapiens	71-75
24574789-8	2014	However, it is still largely unknown whether these methylxanthine derivative-mediated anti-inflammatory effects are associated with the inhibition of CHI3L1-induced cytoplasmic signaling cascades in epithelial cells.	methylxanthine	51-65	chitinase 3 like 1	Homo sapiens	150-156
23403995-6	2012	CONCLUSION: In the present study, there was increase in the levels of ALT, AST enzymes in both saliva and serum levels in the study group as compared to the control group which was statistically significant (p < 0.05) suggesting that long-term exposure of methylxanthines results in impairment of salivary gland antioxidant system which may affect the anticarcinogenic action of saliva.	methylxanthine	259-274	solute carrier family 17 member 5	Homo sapiens	75-78
23985782-0	2014	Chronic administration of the methylxanthine propentofylline impairs reinstatement to cocaine by a GLT-1-dependent mechanism.	methylxanthine	30-44	solute carrier family 1 member 2	Rattus norvegicus	99-104
23996078-0	2013	A pharmacometric approach to investigate the impact of methylxanthine abstinence and caffeine consumption on CYP1A2 activity.	methylxanthine	55-69	cytochrome P450 family 1 subfamily A member 2	Homo sapiens	109-115
23996078-1	2013	This study aimed to investigate the impact of methylxanthine abstinence (MA) periods on CYP1A2 activity in individuals with varying levels of caffeine consumption through development of a population pharmacokinetic model of caffeine and its major metabolite paraxanthine.	methylxanthine	46-60	cytochrome P450 family 1 subfamily A member 2	Homo sapiens	88-94
23580319-5	2013	Bronchodilators, corticosteroids, methylxanthines, phosphodiesterase-4 inhibitors, macrolide antibiotics, mucolytics, and pulmonary rehabilitation improve some outcome measures such as spirometry measures and the frequency of COPD exacerbations without improving mortality.	methylxanthine	34-49	COPD	Homo sapiens	226-230
22673619-0	2012	Noncompetitive blocking of human GLUT1 hexose transporter by methylxanthines reveals an exofacial regulatory binding site.	methylxanthine	61-76	solute carrier family 2 member 1	Homo sapiens	33-38
22859494-10	2012	CONCLUSIONS: The Methyl Xanthine caffeine inhibits the DNA damage response in vitro and in vivo, regulates both cell proliferation and apoptosis after DNA damage, inhibits reactive species, and reduces atherogenesis in ApoE(-/-) mice.	methylxanthine	17-32	apolipoprotein E	Mus musculus	219-223
22673619-4	2012	The displacement of previously bound cytochalasin B revealed a direct interaction between the methylxanthines and GLUT1.	methylxanthine	94-109	solute carrier family 2 member 1	Homo sapiens	114-119
22673619-10	2012	Therefore, the methylxanthine moiety may become an attractive framework for the design of novel specific noncompetitive facilitative GLUT inhibitors.	methylxanthine	15-29	solute carrier family 2 member 1	Homo sapiens	133-137
20103602-11	2010	Our data suggest that the methylxanthine caffeine or its derivative pentoxifylline are promising candidate drugs for the radiosensitization of glioma cells particularly with PTEN mutations.	methylxanthine	26-40	phosphatase and tensin homolog	Homo sapiens	174-178
22420306-1	2012	Chemically, methylxanthine nucleus based Linagliptin (BI-1356, BI-1356-BS) is a dipeptidyl peptidase-IV inhibitor, which has been developed by Boehringer Ingelheim in association with Lilly for the treatment of Type-II Diabetes.	methylxanthine	12-26	dipeptidyl peptidase 4	Homo sapiens	80-103
20859795-3	2011	A number of studies have indicated that methylxanthines also exert effects through alternative mechanisms, in particular via activation of sarcoplasmic reticulum or endoplasmic reticulum ryanodine receptor (RyR) channels.	methylxanthine	40-55	ryanodine receptor 1	Homo sapiens	187-205
20859795-3	2011	A number of studies have indicated that methylxanthines also exert effects through alternative mechanisms, in particular via activation of sarcoplasmic reticulum or endoplasmic reticulum ryanodine receptor (RyR) channels.	methylxanthine	40-55	ryanodine receptor 1	Homo sapiens	207-210
20859795-4	2011	More specifically, RyR channel activation by methylxanthines was reported (1) to stimulate the process of excitation coupling in muscle cells, (2) to augment the excitability of neurons and thus their capacity to release neurotransmitters, and also (3) to improve their survival.	methylxanthine	45-60	ryanodine receptor 1	Homo sapiens	19-22
20859795-5	2011	Here, we address the mechanisms by which methylxanthines control RyR activation and we consider the pharmacological consequences of this activation, in muscle and neuronal cells.	methylxanthine	41-56	ryanodine receptor 1	Homo sapiens	65-68
20859805-4	2011	Based upon the use of specific adenosine receptor antagonists and the observation of a complete loss of diuresis in mice with targeted deletion of the A1AR gene, transport inhibition by methylxanthines is mediated mainly by antagonism of adenosine A1 receptors (A1AR) in the proximal tubule.	methylxanthine	186-201	adenosine A1 receptor	Mus musculus	151-155
20859805-4	2011	Based upon the use of specific adenosine receptor antagonists and the observation of a complete loss of diuresis in mice with targeted deletion of the A1AR gene, transport inhibition by methylxanthines is mediated mainly by antagonism of adenosine A1 receptors (A1AR) in the proximal tubule.	methylxanthine	186-201	adenosine A1 receptor	Mus musculus	262-266
19291178-4	2009	RESULTS: Our data suggest paraxanthine as the most important pharmacological repressor of hepatocellular CTGF expression among the caffeine-derived metabolic methylxanthines with an inhibitory dosage (ID)50 of 1.15 mM, i.e. 3.84-fold lower than what is observed for caffeine.	methylxanthine	158-173	cellular communication network factor 2	Homo sapiens	105-109
19610047-4	2009	New results indicate that the methylxanthine caffeine--a major component of coffee and the most widely consumed pharmacologically active substance in the world--might be responsible for this phenomenon, because it inhibits the synthesis of connective tissue growth factor (CTGF/CCN2) in liver parenchymal and nonparenchymal cells, primarily by inducing degradation of Smad2 (and to a much lesser extent Smad3) and thus impairment of transforming growth factor beta (TGF-beta) signaling.	methylxanthine	30-44	cellular communication network factor 2	Homo sapiens	273-277
19610047-4	2009	New results indicate that the methylxanthine caffeine--a major component of coffee and the most widely consumed pharmacologically active substance in the world--might be responsible for this phenomenon, because it inhibits the synthesis of connective tissue growth factor (CTGF/CCN2) in liver parenchymal and nonparenchymal cells, primarily by inducing degradation of Smad2 (and to a much lesser extent Smad3) and thus impairment of transforming growth factor beta (TGF-beta) signaling.	methylxanthine	30-44	cellular communication network factor 2	Homo sapiens	278-282
19610047-4	2009	New results indicate that the methylxanthine caffeine--a major component of coffee and the most widely consumed pharmacologically active substance in the world--might be responsible for this phenomenon, because it inhibits the synthesis of connective tissue growth factor (CTGF/CCN2) in liver parenchymal and nonparenchymal cells, primarily by inducing degradation of Smad2 (and to a much lesser extent Smad3) and thus impairment of transforming growth factor beta (TGF-beta) signaling.	methylxanthine	30-44	SMAD family member 2	Homo sapiens	368-373
19610047-4	2009	New results indicate that the methylxanthine caffeine--a major component of coffee and the most widely consumed pharmacologically active substance in the world--might be responsible for this phenomenon, because it inhibits the synthesis of connective tissue growth factor (CTGF/CCN2) in liver parenchymal and nonparenchymal cells, primarily by inducing degradation of Smad2 (and to a much lesser extent Smad3) and thus impairment of transforming growth factor beta (TGF-beta) signaling.	methylxanthine	30-44	SMAD family member 3	Homo sapiens	403-408
19610047-4	2009	New results indicate that the methylxanthine caffeine--a major component of coffee and the most widely consumed pharmacologically active substance in the world--might be responsible for this phenomenon, because it inhibits the synthesis of connective tissue growth factor (CTGF/CCN2) in liver parenchymal and nonparenchymal cells, primarily by inducing degradation of Smad2 (and to a much lesser extent Smad3) and thus impairment of transforming growth factor beta (TGF-beta) signaling.	methylxanthine	30-44	transforming growth factor beta 1	Homo sapiens	433-464
19610047-4	2009	New results indicate that the methylxanthine caffeine--a major component of coffee and the most widely consumed pharmacologically active substance in the world--might be responsible for this phenomenon, because it inhibits the synthesis of connective tissue growth factor (CTGF/CCN2) in liver parenchymal and nonparenchymal cells, primarily by inducing degradation of Smad2 (and to a much lesser extent Smad3) and thus impairment of transforming growth factor beta (TGF-beta) signaling.	methylxanthine	30-44	transforming growth factor beta 1	Homo sapiens	466-474
21783975-3	2009	New results indicate that the methylxanthine caffeine, major component of coffee and the most widely consumed pharmacologically active substance in the world, might be responsible for this phenomenon as it, and even more potently its derived primary metabolite paraxanthine, inhibits transforming growth factor (TGF)-beta-dependent and -independent synthesis of connective tissue growth factor (CTGF/CCN2) in liver parenchymal cells in vitro and in vivo.	methylxanthine	30-44	cellular communication network factor 2	Homo sapiens	395-399
21783975-3	2009	New results indicate that the methylxanthine caffeine, major component of coffee and the most widely consumed pharmacologically active substance in the world, might be responsible for this phenomenon as it, and even more potently its derived primary metabolite paraxanthine, inhibits transforming growth factor (TGF)-beta-dependent and -independent synthesis of connective tissue growth factor (CTGF/CCN2) in liver parenchymal cells in vitro and in vivo.	methylxanthine	30-44	cellular communication network factor 2	Homo sapiens	400-404
20201780-1	2010	The aim of this study was to assess the impact of a P-glycoprotein and CYP3A inhibitor, verapamil on the pharmacokinetics of two methylxanthines, pentoxifylline and lisofylline in male CD-1 mice.	methylxanthine	129-144	cytochrome P450, family 3, subfamily a, polypeptide 11	Mus musculus	71-76
18518861-9	2008	Furthermore, as with caffeine, the clinically relevant, pro-arrhythmic methylxanthines aminophylline and theophylline potentiated luminal Ca(2+) activation of RyR2, and increased the propensity for spontaneous Ca(2+) release, mimicking the effects of disease-linked RyR2 mutations.	methylxanthine	71-86	ryanodine receptor 2	Homo sapiens	159-163
19018984-3	2009	Recently, we demonstrated that the methylxanthine derivate caffeine leads to an upregulation of peroxisome proliferator activated receptor gamma (PPARgamma) expression in hepatocytes, thus sensitizing these cells to the well-known inhibitory effect of 15-deoxy-Delta(12,14)-prostaglandin J(2) (15-d-PGJ(2)) on CTGF expression.	methylxanthine	35-49	peroxisome proliferator activated receptor gamma	Homo sapiens	96-144
19018984-3	2009	Recently, we demonstrated that the methylxanthine derivate caffeine leads to an upregulation of peroxisome proliferator activated receptor gamma (PPARgamma) expression in hepatocytes, thus sensitizing these cells to the well-known inhibitory effect of 15-deoxy-Delta(12,14)-prostaglandin J(2) (15-d-PGJ(2)) on CTGF expression.	methylxanthine	35-49	peroxisome proliferator activated receptor gamma	Homo sapiens	146-155
19018984-3	2009	Recently, we demonstrated that the methylxanthine derivate caffeine leads to an upregulation of peroxisome proliferator activated receptor gamma (PPARgamma) expression in hepatocytes, thus sensitizing these cells to the well-known inhibitory effect of 15-deoxy-Delta(12,14)-prostaglandin J(2) (15-d-PGJ(2)) on CTGF expression.	methylxanthine	35-49	cellular communication network factor 2	Homo sapiens	310-314
19018984-8	2009	CONCLUSIONS: In conclusion, our data thus proposed an increased suitability of these patient groups for therapeutic approaches with drugs inducing PPARgamma expression, such as methylxanthine derivates.	methylxanthine	177-191	peroxisome proliferator activated receptor gamma	Homo sapiens	147-156
18518861-9	2008	Furthermore, as with caffeine, the clinically relevant, pro-arrhythmic methylxanthines aminophylline and theophylline potentiated luminal Ca(2+) activation of RyR2, and increased the propensity for spontaneous Ca(2+) release, mimicking the effects of disease-linked RyR2 mutations.	methylxanthine	71-86	ryanodine receptor 2	Homo sapiens	266-270
14747882-1	2004	BACKGROUND AND OBJECTIVE: The standard approach for phenotyping of the human arylamine N-acetyltransferase 2 (NAT2) uses urinary caffeine metabolite ratios after a caffeine test dose taken in after methylxanthine abstinence.	methylxanthine	198-212	N-acetyltransferase 2	Homo sapiens	77-108
15998294-2	2005	In maternal brain, radioligand binding assays showed that chronic treatment with methylxanthines caused a significant decrease in the total number of mGluRs.	methylxanthine	81-96	glutamate metabotropic receptor 1	Rattus norvegicus	150-156
15998294-4	2005	Immunodetection showed that mGluR1a and phospholipase C beta1 (PLCbeta1) were significantly decreased in response to chronic methylxanthine treatment, whereas alphaG(q/11) was not affected.	methylxanthine	125-139	glutamate metabotropic receptor 1	Rattus norvegicus	28-34
15998294-4	2005	Immunodetection showed that mGluR1a and phospholipase C beta1 (PLCbeta1) were significantly decreased in response to chronic methylxanthine treatment, whereas alphaG(q/11) was not affected.	methylxanthine	125-139	phospholipase C beta 1	Rattus norvegicus	40-61
15998294-4	2005	Immunodetection showed that mGluR1a and phospholipase C beta1 (PLCbeta1) were significantly decreased in response to chronic methylxanthine treatment, whereas alphaG(q/11) was not affected.	methylxanthine	125-139	phospholipase C beta 1	Rattus norvegicus	63-71
15466201-3	2004	The methylxanthine caffeine and the staurosporine analog UCN-01, which can inhibit ATM and Chk kinases, efficiently abrogated the IR-induced G(2)-M arrest and induced mitochondrial activation as judged by the loss of the mitochondrial membrane potential and the release of cytochrome c and Smac/Diablo.	methylxanthine	4-18	ATM serine/threonine kinase	Homo sapiens	83-86
15466201-3	2004	The methylxanthine caffeine and the staurosporine analog UCN-01, which can inhibit ATM and Chk kinases, efficiently abrogated the IR-induced G(2)-M arrest and induced mitochondrial activation as judged by the loss of the mitochondrial membrane potential and the release of cytochrome c and Smac/Diablo.	methylxanthine	4-18	choline kinase alpha	Homo sapiens	91-94
15466201-3	2004	The methylxanthine caffeine and the staurosporine analog UCN-01, which can inhibit ATM and Chk kinases, efficiently abrogated the IR-induced G(2)-M arrest and induced mitochondrial activation as judged by the loss of the mitochondrial membrane potential and the release of cytochrome c and Smac/Diablo.	methylxanthine	4-18	cytochrome c, somatic	Homo sapiens	273-285
15466201-3	2004	The methylxanthine caffeine and the staurosporine analog UCN-01, which can inhibit ATM and Chk kinases, efficiently abrogated the IR-induced G(2)-M arrest and induced mitochondrial activation as judged by the loss of the mitochondrial membrane potential and the release of cytochrome c and Smac/Diablo.	methylxanthine	4-18	diablo IAP-binding mitochondrial protein	Homo sapiens	290-294
15466201-3	2004	The methylxanthine caffeine and the staurosporine analog UCN-01, which can inhibit ATM and Chk kinases, efficiently abrogated the IR-induced G(2)-M arrest and induced mitochondrial activation as judged by the loss of the mitochondrial membrane potential and the release of cytochrome c and Smac/Diablo.	methylxanthine	4-18	diablo IAP-binding mitochondrial protein	Homo sapiens	295-301
16979558-7	2006	The Gr66a mutant exhibited normal tastant-induced action potentials upon presentation of theobromine, a methylxanthine in cocoa.	methylxanthine	104-118	Gustatory receptor 66a	Drosophila melanogaster	4-9
16729716-5	2006	Methylxanthines are non-selective phosphodiesterase (PDE) inhibitors with bronchodilatory and anti-inflammatory effects; however, their use in COPD and other respiratory conditions is limited by their narrow therapeutic index and poor safety profile.	methylxanthine	0-15	COPD	Homo sapiens	143-147
16156128-1	2005	Pentoxifylline (PTX, a methylxanthine derivative) has been found to interrupt early gene activation for tumour necrosis factor, interleukin-1, interleukin-6 and tissue factor production and to improve survival from experimental sepsis.	methylxanthine	23-37	interleukin-6	Oryctolagus cuniculus	143-156
16156128-1	2005	Pentoxifylline (PTX, a methylxanthine derivative) has been found to interrupt early gene activation for tumour necrosis factor, interleukin-1, interleukin-6 and tissue factor production and to improve survival from experimental sepsis.	methylxanthine	23-37	tissue factor	Oryctolagus cuniculus	161-174
14747882-1	2004	BACKGROUND AND OBJECTIVE: The standard approach for phenotyping of the human arylamine N-acetyltransferase 2 (NAT2) uses urinary caffeine metabolite ratios after a caffeine test dose taken in after methylxanthine abstinence.	methylxanthine	198-212	N-acetyltransferase 2	Homo sapiens	110-114
12542900-2	2002	It has been reported that theophylline was metabolized to 1,3-dimethyluric acid by CYP1A2 and CYP2E1 and 1-methylxanthine via CYP1A2, which was metabolized further to 1-methyluric acid via xanthine oxidase in rats.	methylxanthine	107-121	cytochrome P450, family 2, subfamily e, polypeptide 1	Rattus norvegicus	94-106
14757500-8	2004	The multiple linear regression for effectiveness of methylxanthines in reversal of P-gp mediated MDR of L1210/VCR cells (expressed as respective IC(50r) values) has been computed, with molar weight: M(w), molar volume: V(M), molar refractivity: R(M), crystal density: d and partition coefficient n-octanol/water: logP as descriptors.	methylxanthine	52-67	phosphoglycolate phosphatase	Mus musculus	83-87
12807744-3	2003	Interestingly, the methylxanthine caffeine can abrogate the p53 accumulation induced by certain DNA-damaging agents by an unknown mechanism.	methylxanthine	19-33	tumor protein p53	Homo sapiens	60-63
12844341-3	2003	Pentoxifylline, a methylxanthine usually used in the treatment of peripheral arterial circulatory disorders, has been reported to inhibit TNF-alpha synthesis.	methylxanthine	18-32	tumor necrosis factor	Rattus norvegicus	138-147
12542900-2	2002	It has been reported that theophylline was metabolized to 1,3-dimethyluric acid by CYP1A2 and CYP2E1 and 1-methylxanthine via CYP1A2, which was metabolized further to 1-methyluric acid via xanthine oxidase in rats.	methylxanthine	107-121	cytochrome P450, family 1, subfamily a, polypeptide 2	Rattus norvegicus	126-132
12055093-4	2002	Insulin-stimulated leptin secretion could also be inhibited by a series of agents increasing intracellular cAMP levels, such as lipolytic hormones (ACTH and thyrotropin-stimulating hormone), various nonhydrolyzable cAMP analogs, pertussis toxin, forskolin, methylxanthines (caffeine, theophylline, IBMX), and specific inhibitors of phosphodiesterase III (imazodan, milrinone, and amrinone).	methylxanthine	257-272	leptin	Rattus norvegicus	19-25
12153486-1	2002	Pregnant rats were treated daily with 1 g/L of caffeine or theophylline in their drinking water during pregnancy and the effect of these methylxanthines on adenosine A1 receptor was assayed using binding and reverse transcription polymerase chain reaction (RT-PCR) assays in brains from both mothers and full-term fetuses.	methylxanthine	137-152	adenosine A1 receptor	Rattus norvegicus	156-177
12587528-2	2002	Pentoxifylline, a methylxanthine derivative, was found to inhibit TNF-alpha synthesis.	methylxanthine	18-32	tumor necrosis factor	Oryctolagus cuniculus	66-75
11812656-2	2002	As treatment with the methylxanthine theophylline, a nonspecific PDE inhibitor, induces apoptosis in leukemic cells from patients with the B-lineage malignancy chronic lymphocytic leukemia (CLL), we sought to determine if PDE7A was a target of theophylline therapy in such cells.	methylxanthine	22-36	phosphodiesterase 7A	Homo sapiens	222-227
11812656-4	2002	Among the six cAMP PDEs (PDE1B, PDE3B, PDE4A, PDE4B, PDE4D, and PDE7) examined in WSU-CLL, only PDE7A levels were augmented by treatment with methylxanthines.	methylxanthine	142-157	phosphodiesterase 1B	Homo sapiens	25-30
11812656-4	2002	Among the six cAMP PDEs (PDE1B, PDE3B, PDE4A, PDE4B, PDE4D, and PDE7) examined in WSU-CLL, only PDE7A levels were augmented by treatment with methylxanthines.	methylxanthine	142-157	phosphodiesterase 3B	Homo sapiens	32-37
11812656-4	2002	Among the six cAMP PDEs (PDE1B, PDE3B, PDE4A, PDE4B, PDE4D, and PDE7) examined in WSU-CLL, only PDE7A levels were augmented by treatment with methylxanthines.	methylxanthine	142-157	phosphodiesterase 4A	Homo sapiens	39-44
11812656-4	2002	Among the six cAMP PDEs (PDE1B, PDE3B, PDE4A, PDE4B, PDE4D, and PDE7) examined in WSU-CLL, only PDE7A levels were augmented by treatment with methylxanthines.	methylxanthine	142-157	phosphodiesterase 4B	Homo sapiens	46-51
11812656-4	2002	Among the six cAMP PDEs (PDE1B, PDE3B, PDE4A, PDE4B, PDE4D, and PDE7) examined in WSU-CLL, only PDE7A levels were augmented by treatment with methylxanthines.	methylxanthine	142-157	phosphodiesterase 4D	Homo sapiens	53-58
11812656-4	2002	Among the six cAMP PDEs (PDE1B, PDE3B, PDE4A, PDE4B, PDE4D, and PDE7) examined in WSU-CLL, only PDE7A levels were augmented by treatment with methylxanthines.	methylxanthine	142-157	phosphodiesterase 7A	Homo sapiens	64-68
11812656-4	2002	Among the six cAMP PDEs (PDE1B, PDE3B, PDE4A, PDE4B, PDE4D, and PDE7) examined in WSU-CLL, only PDE7A levels were augmented by treatment with methylxanthines.	methylxanthine	142-157	phosphodiesterase 7A	Homo sapiens	96-101
11465391-0	2001	Inhibition of human CYP1A2 activity in vitro by methylxanthines: potent competitive inhibition by 8-phenyltheophylline.	methylxanthine	48-63	cytochrome P450 family 1 subfamily A member 2	Homo sapiens	20-26
11477212-0	2001	Glucose transporter type 1 deficiency syndrome (Glut1DS): methylxanthines potentiate GLUT1 haploinsufficiency in vitro.	methylxanthine	58-73	solute carrier family 2 member 1	Homo sapiens	48-55
11477212-0	2001	Glucose transporter type 1 deficiency syndrome (Glut1DS): methylxanthines potentiate GLUT1 haploinsufficiency in vitro.	methylxanthine	58-73	solute carrier family 2 member 1	Homo sapiens	85-90
11477212-11	2001	Our study suggests that Glut1DS patients may have a reduced safety margin for methylxanthines.	methylxanthine	78-93	solute carrier family 2 member 1	Homo sapiens	24-31
11477212-12	2001	Consumption of methylxanthine-containing products may aggravate the neurologic symptoms associated with the Glut1DS.	methylxanthine	15-29	solute carrier family 2 member 1	Homo sapiens	108-115
11677656-8	2001	Interestingly, caffeine and other methyl xanthines preferentially radiosensitize cells that lack normal p53 function.	methylxanthine	34-50	tumor protein p53	Homo sapiens	104-107
10996031-1	2000	Pentoxifylline (PTX), a methylxanthine derivative, has been reported to be an effective drug in inhibiting TNF-alpha responses during septic shock.	methylxanthine	24-38	tumor necrosis factor	Mus musculus	107-116
10836732-3	2000	Recently inhibition of the sodium/hydrogen exchanger isozyme-1 (NHE-1) has been shown to be equal to IPC at providing myocardial protection in dogs and may be an alternative to IPC in patients taking sulfonylureas or methylxanthines.	methylxanthine	217-232	solute carrier family 9 member A1	Canis lupus familiaris	64-69
10836732-6	2000	NHE-1 inhibition and IPC do not overlap pharmacologically, and NHE-1 inhibition may be an alternative for cardioprotection in patients taking sulfonylureas or methylxanthines.	methylxanthine	159-174	solute carrier family 9 member A1	Homo sapiens	63-68
9698467-2	1998	The possibility that such an agent could be directed specifically against p53-defective tumor cells led us to study the new methylxanthine, Lisofylline, for its ability to sensitize ovary cancer cells to cis-diamminedichloroplatinum(II) (CDDP).	methylxanthine	124-138	tumor protein p53	Homo sapiens	74-77
9852118-4	1998	In contrast, the cAMP phosphodiesterase inhibitor, theophylline, inhibited mTOR activity not only when added to intact adipocytes but also when added to immunopurified mTOR in vitro, demonstrating that certain methylxanthines are able to inhibit mTOR independently of increasing cAMP.	methylxanthine	210-225	mechanistic target of rapamycin kinase	Homo sapiens	75-79
10741643-3	2000	A prior study demonstrated that the expression of the cyclin B1 protein is reduced by irradiation, and restored to control levels by the methylxanthine drug pentoxifylline, which is a potent G2 block abrogator.	methylxanthine	137-151	cyclin B1	Homo sapiens	54-63
10694235-2	2000	We have previously shown that ATP increased cyclic AMP in NG108-15 cells, which was inhibited by P(1) receptor antagonist methylxanthines.	methylxanthine	122-137	zinc finger protein 185	Mus musculus	97-101
10321674-1	1999	OBJECTIVE: To evaluate the influence of the methylxanthine derivative, pentoxifylline, on plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6 in prematurely delivered infants with generalized bacterial infections and to assess the effect of this immunomodulating drug on the clinical outcome in newborns with sepsis.	methylxanthine	44-58	tumor necrosis factor	Homo sapiens	107-140
10321674-1	1999	OBJECTIVE: To evaluate the influence of the methylxanthine derivative, pentoxifylline, on plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6 in prematurely delivered infants with generalized bacterial infections and to assess the effect of this immunomodulating drug on the clinical outcome in newborns with sepsis.	methylxanthine	44-58	interleukin 6	Homo sapiens	166-170
9354686-8	1997	A dosedependent inhibition of PMA-induced VEGF secretion was observed when the cells were incubated in the presence of pentoxifylline, a methylxanthine known to inhibit neutrophil degranulation.	methylxanthine	137-151	vascular endothelial growth factor A	Homo sapiens	42-46
9669475-2	1998	Pentoxifylline (PTX) is a methylxanthine derivative that inhibits the production of TNF-alpha, a cytokine involved in EAE and multiple sclerosis physiopathology.	methylxanthine	26-40	tumor necrosis factor	Rattus norvegicus	84-93
10467435-1	1997	Caffeine, an important member of methylxanthines, induced a prolonged nocturnal rise in pineal melatonin content and an increase in its rate-limiting enzyme serotonin N-acetyltransferase (NAT) activity.	methylxanthine	33-48	aralkylamine N-acetyltransferase	Rattus norvegicus	157-186
10467435-1	1997	Caffeine, an important member of methylxanthines, induced a prolonged nocturnal rise in pineal melatonin content and an increase in its rate-limiting enzyme serotonin N-acetyltransferase (NAT) activity.	methylxanthine	33-48	N-acetyltransferase 1	Rattus norvegicus	188-191
9094673-7	1997	Vpr-mediated G2 arrest was alleviated by methylxanthines at concentrations similar to those needed to reverse the G2 arrest induced by HN2, and cells proceeded apparently normally through at least one complete cell cycle.	methylxanthine	41-56	Vpr	Human immunodeficiency virus 1	0-3
9160673-4	1997	In order to prevent this TNF alpha associated HCMV reactivation patients were additionally treated with pentoxifylline (PTX), a methylxanthine derivative that has been shown to suppress TNF alpha induction.	methylxanthine	128-142	tumor necrosis factor	Homo sapiens	186-195
9067700-4	1997	Pentoxifylline is a methylxanthine derivative suppressing the release of TNF alpha.	methylxanthine	20-34	tumor necrosis factor	Homo sapiens	73-82
9172017-1	1996	Pentoxifylline (PTX) is a methylxanthine drug known to inhibit the production of tumor necrosis factor-alpha (TNF alpha), which plays a key role in inflammation.	methylxanthine	26-40	tumor necrosis factor	Homo sapiens	81-108
9343951-7	1997	Methylxanthines (caffeine and theophylline) as well as "classical" calcium-mobilizing agents (ionomycin and thapsigargin) inhibited the expression of VCAM-1 in MME.	methylxanthine	0-15	vascular cell adhesion molecule 1	Mus musculus	150-156
9343951-7	1997	Methylxanthines (caffeine and theophylline) as well as "classical" calcium-mobilizing agents (ionomycin and thapsigargin) inhibited the expression of VCAM-1 in MME.	methylxanthine	0-15	membrane metallo endopeptidase	Mus musculus	160-163
9172017-1	1996	Pentoxifylline (PTX) is a methylxanthine drug known to inhibit the production of tumor necrosis factor-alpha (TNF alpha), which plays a key role in inflammation.	methylxanthine	26-40	tumor necrosis factor	Homo sapiens	110-119
9089006-1	1996	Pentoxifylline (PTX), a methylxanthine derivative, is known to inhibit the production of the TH1 cytokines interleukin-2, tumour necrosis factor-alpha and interferon-gamma.	methylxanthine	24-38	negative elongation factor complex member C/D, Th1l	Mus musculus	93-96
9089006-1	1996	Pentoxifylline (PTX), a methylxanthine derivative, is known to inhibit the production of the TH1 cytokines interleukin-2, tumour necrosis factor-alpha and interferon-gamma.	methylxanthine	24-38	interleukin 2	Mus musculus	107-150
9089006-1	1996	Pentoxifylline (PTX), a methylxanthine derivative, is known to inhibit the production of the TH1 cytokines interleukin-2, tumour necrosis factor-alpha and interferon-gamma.	methylxanthine	24-38	interferon gamma	Mus musculus	155-171
8786577-4	1996	Infusion of these methylxanthines into livers from mice pretreated with lipopolysaccharide or TNF also inhibited TNF release in an immediate and reversible way even after TNF production had been initiated.	methylxanthine	18-33	tumor necrosis factor	Mus musculus	94-97
8887654-1	1996	Mitogen-induced activation of p70(s6k) is associated with the phosphorylation of specific sites which are negatively affected by the immunosuppressant rapamycin, the fungal metabolite wortmannin, and the methylxanthine SQ20006.	methylxanthine	204-218	ubiquitin associated and SH3 domain containing B	Homo sapiens	30-33
8865286-1	1996	Pentoxifylline (PTXF) is a methylxanthine derivative which modifies leukocyte function and inhibits tumor necrosis factor (TNF)-alpha release.	methylxanthine	27-41	tumor necrosis factor	Homo sapiens	100-133
8764378-0	1996	Enhanced release of interleukin-10 and soluble tumor necrosis factor receptors as novel principles of methylxanthine action in murine models of endotoxic shock.	methylxanthine	102-116	interleukin 10	Mus musculus	20-34
8764378-0	1996	Enhanced release of interleukin-10 and soluble tumor necrosis factor receptors as novel principles of methylxanthine action in murine models of endotoxic shock.	methylxanthine	102-116	tumor necrosis factor	Mus musculus	47-68
8764378-3	1996	The methylxanthines attenuated systemic release of endogenous tumor necrosis factor (TNF) and interferon-gamma during endotoxic shock, and potently up-regulated early production of circulating interleukin-10 and interleukin-6.	methylxanthine	4-19	tumor necrosis factor	Mus musculus	62-83
8764378-3	1996	The methylxanthines attenuated systemic release of endogenous tumor necrosis factor (TNF) and interferon-gamma during endotoxic shock, and potently up-regulated early production of circulating interleukin-10 and interleukin-6.	methylxanthine	4-19	tumor necrosis factor	Mus musculus	85-88
8764378-3	1996	The methylxanthines attenuated systemic release of endogenous tumor necrosis factor (TNF) and interferon-gamma during endotoxic shock, and potently up-regulated early production of circulating interleukin-10 and interleukin-6.	methylxanthine	4-19	interferon gamma	Mus musculus	94-110
8764378-3	1996	The methylxanthines attenuated systemic release of endogenous tumor necrosis factor (TNF) and interferon-gamma during endotoxic shock, and potently up-regulated early production of circulating interleukin-10 and interleukin-6.	methylxanthine	4-19	interleukin 10	Mus musculus	193-207
8764378-3	1996	The methylxanthines attenuated systemic release of endogenous tumor necrosis factor (TNF) and interferon-gamma during endotoxic shock, and potently up-regulated early production of circulating interleukin-10 and interleukin-6.	methylxanthine	4-19	interleukin 6	Mus musculus	212-225
8764378-8	1996	We concluded that, in addition to a direct target cell protection via an increase in intracellular cAMP, methylxanthines prevented the systemic toxicity of LPS in mice by a further principle, i.e., by a shift of the humoral response to LPS in favor of an enhanced release of immunosuppressive cytokines.	methylxanthine	105-120	toll-like receptor 4	Mus musculus	156-159
8764378-8	1996	We concluded that, in addition to a direct target cell protection via an increase in intracellular cAMP, methylxanthines prevented the systemic toxicity of LPS in mice by a further principle, i.e., by a shift of the humoral response to LPS in favor of an enhanced release of immunosuppressive cytokines.	methylxanthine	105-120	toll-like receptor 4	Mus musculus	236-239
8786577-0	1996	Tumor necrosis factor production in the perfused mouse liver and its pharmacological modulation by methylxanthines.	methylxanthine	99-114	tumor necrosis factor	Mus musculus	0-21
8786577-4	1996	Infusion of these methylxanthines into livers from mice pretreated with lipopolysaccharide or TNF also inhibited TNF release in an immediate and reversible way even after TNF production had been initiated.	methylxanthine	18-33	tumor necrosis factor	Mus musculus	113-116
8786577-4	1996	Infusion of these methylxanthines into livers from mice pretreated with lipopolysaccharide or TNF also inhibited TNF release in an immediate and reversible way even after TNF production had been initiated.	methylxanthine	18-33	tumor necrosis factor	Mus musculus	113-116
7530274-7	1995	Taken together, these observations suggest interferons and methylxanthines may inhibit fibroblast collagen synthesis by a common mechanism requiring new protein synthesis that suppresses procollagen gene transcription through down-regulation of NF-1.	methylxanthine	59-74	neurofibromin 1	Homo sapiens	245-249
7545671-0	1995	Rapamycin, wortmannin, and the methylxanthine SQ20006 inactivate p70s6k by inducing dephosphorylation of the same subset of sites.	methylxanthine	31-45	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	65-71
7545671-7	1995	However, other agents that raise intracellular cAMP levels have no inhibitory effect, leading to the hypothesis that the inhibitory actions of methylxanthines on p70s6k activity are not through activating protein kinase A but through inhibition of an upstream kinase.	methylxanthine	143-158	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	162-168
7545671-8	1995	Together the results indicate that there are two kinase signaling pathways that must converge to activate p70s6k and that only one of these pathways is sensitive to rapamycin, wortmannin, and methylxanthine inhibition.	methylxanthine	192-206	ribosomal protein S6 kinase, polypeptide 1	Mus musculus	106-112
8655288-0	1995	Methylxanthines with adenosine alter TNF alpha-primed PMN activation.	methylxanthine	0-15	tumor necrosis factor	Homo sapiens	37-46
8655288-6	1995	These activities of the methylxanthines were only observed in the presence of physiological concentrations of adenosine, and were abolished by the treatment of the PMN with adenosine deaminase.	methylxanthine	24-39	adenosine deaminase	Homo sapiens	173-192
7835945-1	1994	Pentoxifylline (PTX) is a methylxanthine compound known to inhibit the production of tumour necrosis factor-alpha (TNF-alpha), which is an important inflammatory mediator.	methylxanthine	26-40	tumor necrosis factor	Homo sapiens	115-124
7640043-2	1995	Preclinical studies show that pentoxifylline (PTXF), a methylxanthine derivative, inhibits IL-2 toxicity while preserving anti-tumour efficacy.	methylxanthine	55-69	interleukin 2	Homo sapiens	91-95
7988727-3	1994	We report the inhibitory effect of interleukin 10 (IL-10) and that of pentoxifylline, a methyl xanthine derivative, on monocyte expression of TF activity, TF protein and TF mRNA in response to CRP.	methylxanthine	88-103	coagulation factor III, tissue factor	Homo sapiens	142-144
7988727-3	1994	We report the inhibitory effect of interleukin 10 (IL-10) and that of pentoxifylline, a methyl xanthine derivative, on monocyte expression of TF activity, TF protein and TF mRNA in response to CRP.	methylxanthine	88-103	C-reactive protein	Homo sapiens	193-196
7986202-11	1994	Our studies suggest that agents that can increase plasma adenosine levels (e.g. inhibitors of adenosine uptake and adenosine metabolism) or methylxanthines may be useful in altering (inhibiting or enhancing, respectively) PAF actions on platelets and other tissues.	methylxanthine	140-155	PCNA clamp associated factor	Homo sapiens	222-225
7986202-3	1994	In addition, the effects of methylxanthines (e.g. theophylline and caffeine) were studied on PAF-induced platelet aggregation in PRP isolated from blood samples from healthy subjects.	methylxanthine	28-43	PCNA clamp associated factor	Homo sapiens	93-96
8063218-2	1994	Pentoxifylline, a methylxanthine derivative, prevents leukocyte adherence to vascular endothelium and protects organs from shock by reducing tumour necrosis factor alpha (TNF alpha) concentrations.	methylxanthine	18-32	tumor necrosis factor	Rattus norvegicus	171-180
8012963-2	1994	Pentoxifylline (PTX) is a methylxanthine which reduces IL-2 toxicity in animals.	methylxanthine	26-40	interleukin 2	Homo sapiens	55-59
8119047-5	1993	Some quinolones preferentially inhibit CYP1A2, which is partially responsible for methylxanthine metabolism.	methylxanthine	82-96	cytochrome P450 family 1 subfamily A member 2	Homo sapiens	39-45
7514535-0	1994	Methylxanthines and calcium-mobilizing agents inhibit the expression of cytokine-inducible nitric oxide synthase and vascular cell adhesion molecule-1 in murine microvascular endothelial cells.	methylxanthine	0-15	nitric oxide synthase 2, inducible	Mus musculus	81-112
7514535-0	1994	Methylxanthines and calcium-mobilizing agents inhibit the expression of cytokine-inducible nitric oxide synthase and vascular cell adhesion molecule-1 in murine microvascular endothelial cells.	methylxanthine	0-15	vascular cell adhesion molecule 1	Mus musculus	117-150
7514535-7	1994	Methylxanthines (caffeine and theophylline) as well as several calcium-mobilizing agents inhibited the expression/activity of both iNOS and VCAM-1 in MME.	methylxanthine	0-15	nitric oxide synthase 2, inducible	Mus musculus	131-135
7514535-7	1994	Methylxanthines (caffeine and theophylline) as well as several calcium-mobilizing agents inhibited the expression/activity of both iNOS and VCAM-1 in MME.	methylxanthine	0-15	vascular cell adhesion molecule 1	Mus musculus	140-146
8019755-25	1994	The evidence suggests, instead, that PDA facilitates methylxanthine- or ryanodine-induced release of Ca2+ from the intracellular store.	methylxanthine	53-67	LOW QUALITY PROTEIN: carbonic anhydrase 2	Cavia porcellus	101-104
8218378-4	1993	scavenging by pentoxifylline (Ptx, a methylxanthine), uric acid and thymine on the OH.-induced alterations of a protein, lysozyme.	methylxanthine	37-51	lysozyme	Homo sapiens	121-129
8409522-3	1993	Pentoxifylline, a methylxanthine derivative used in the treatment of vascular disorders, currently has been found to suppress the production of tumor necrosis factor alpha by human and murine leukocytes.	methylxanthine	18-32	tumor necrosis factor	Homo sapiens	144-171
8213066-1	1993	Pentoxifylline, a widely used methylxanthine, has been proven to inhibit the production and action of the cytokine TNF alpha.	methylxanthine	30-44	tumor necrosis factor	Rattus norvegicus	115-124
1356929-6	1992	In vitro investigations with each of the four methylxanthines showed two of these metabolites to be most effective at reducing PMN respiratory burst activity, lactoferrin release, and the expression of CD11b and CD18 molecules.	methylxanthine	46-61	integrin subunit alpha M	Homo sapiens	202-207
7682199-4	1993	Pentoxifylline, a methylxanthine derivative with phosphodiesterase inhibitory activity, selectively inhibited LPS-induced TNF alpha release with an IC50 of 100 microM.	methylxanthine	18-32	tumor necrosis factor	Homo sapiens	122-131
7678547-3	1993	Pentoxifylline, a substituted methylxanthine approved for treatment of intermittent claudication, has been shown in preclinical studies to down-regulate TNF RNA expression as well as TNF activity.	methylxanthine	30-44	tumor necrosis factor	Homo sapiens	153-156
7678547-3	1993	Pentoxifylline, a substituted methylxanthine approved for treatment of intermittent claudication, has been shown in preclinical studies to down-regulate TNF RNA expression as well as TNF activity.	methylxanthine	30-44	tumor necrosis factor	Homo sapiens	183-186
1356929-6	1992	In vitro investigations with each of the four methylxanthines showed two of these metabolites to be most effective at reducing PMN respiratory burst activity, lactoferrin release, and the expression of CD11b and CD18 molecules.	methylxanthine	46-61	integrin subunit beta 2	Homo sapiens	212-216
1281035-5	1992	Although their mechanism of action is unknown, one class of compounds, the methylxanthines, have been shown to reverse a fundamental CF abnormality in CF salivary cells and in non-epithelial cells overexpressing CFTR.	methylxanthine	75-90	CF transmembrane conductance regulator	Homo sapiens	212-216
1319356-0	1992	Interaction of methyl-xanthines with myeloperoxidase.	methylxanthine	15-31	myeloperoxidase	Homo sapiens	37-52
1709825-0	1991	Pentoxifylline and other methyl xanthines inhibit interleukin-2 receptor expression in human lymphocytes.	methylxanthine	25-41	interleukin 2 receptor subunit alpha	Homo sapiens	50-72
1385797-1	1992	Pentoxifylline (PTX) is a methylxanthine compound known to inhibit the production of tumour necrosis factor-alpha (TNF-alpha) by monocytic cells.	methylxanthine	26-40	tumor necrosis factor	Homo sapiens	115-124
1652591-1	1991	We have demonstrated previously that a variety of agents including corticosteroids, thyroid hormone, cationophores, methylxanthines, and analogues of cAMP--all of which have diversified functions in various tissues--elevate cellular angiotensin converting enzyme (ACE) activity of bovine endothelial cells in culture.	methylxanthine	116-131	angiotensin I converting enzyme	Bos taurus	233-262
1652591-1	1991	We have demonstrated previously that a variety of agents including corticosteroids, thyroid hormone, cationophores, methylxanthines, and analogues of cAMP--all of which have diversified functions in various tissues--elevate cellular angiotensin converting enzyme (ACE) activity of bovine endothelial cells in culture.	methylxanthine	116-131	angiotensin I converting enzyme	Bos taurus	264-267
1709825-8	1991	The inhibitory effect on IL-2R expression was also noted with other methylxanthines, theophylline and isobutylmethylxanthine, and with dbcAMP and forskolin.	methylxanthine	68-83	interleukin 2 receptor subunit alpha	Homo sapiens	25-30
2005584-3	1991	Caffeine may be particularly troublesome in this regard because this methylxanthine has central nervous system effects and intracellular actions that also might contribute to the overall ability of caffeine to potentiate renin secretion.	methylxanthine	69-83	renin	Rattus norvegicus	221-226
35630553-2	2022	Its general structure has already been experimentally resolved, but the binding site of TRPA1 antagonists such as HC-030031, a model methylxanthine derivative, remains unknown.	methylxanthine	133-147	transient receptor potential cation channel subfamily A member 1	Homo sapiens	88-93
2173454-2	1990	Pentoxifylline (PTX), a methylxanthine, protects against TNF-induced and sepsis-induced acute lung injury in vivo.	methylxanthine	24-38	tumor necrosis factor	Bos taurus	57-60
2299585-9	1990	The most likely mechanisms for the effects observed are 1) inhibition of acetaminophen reactive metabolite formation in 3-methylcholanthrene-induced animals by each of the methylxanthines, and 2) activation of the phenobarbital-inducible forms of cytochrome(s) P-450 toward formation of acetaminophen reactive metabolites by caffeine and theophylline, but not theobromine.	methylxanthine	172-187	VPS52 subunit of GARP complex	Rattus norvegicus	52-57
34831035-5	2021	Using minigene approaches and patient cells, we here show that methylxanthine derivatives and the food-derived flavonoid luteolin are able to enhance the correct splicing of the AGA mRNA with a splice-site mutation c.128-2A>G in aspartylglucosaminuria, and result in increased AGA enzyme activity in patient cells.	methylxanthine	63-77	aspartylglucosaminidase	Homo sapiens	178-181
34831035-5	2021	Using minigene approaches and patient cells, we here show that methylxanthine derivatives and the food-derived flavonoid luteolin are able to enhance the correct splicing of the AGA mRNA with a splice-site mutation c.128-2A>G in aspartylglucosaminuria, and result in increased AGA enzyme activity in patient cells.	methylxanthine	63-77	aspartylglucosaminidase	Homo sapiens	277-280
2165398-1	1990	Induction of C-reactive protein (CRP) by conditioned medium from lipopolysaccharide-stimulated human monocytes in two human hepatoma-cell lines, Hep 3B and NPLC/PRF/5, was potentiated 3-6-fold by the methylxanthine caffeine.	methylxanthine	200-214	C-reactive protein	Homo sapiens	13-31
2165398-1	1990	Induction of C-reactive protein (CRP) by conditioned medium from lipopolysaccharide-stimulated human monocytes in two human hepatoma-cell lines, Hep 3B and NPLC/PRF/5, was potentiated 3-6-fold by the methylxanthine caffeine.	methylxanthine	200-214	C-reactive protein	Homo sapiens	33-36
1692607-2	1990	Chronic exposure of cultures to GABA, benzodiazepines, or methylxanthines results in decreased enhancement of [3H]flunitrazepam binding by GABA, consistent with an allosteric uncoupling of GABA and benzodiazepine recognition sites of the GABAA receptor.	methylxanthine	58-73	gamma-aminobutyric acid type A receptor gamma3 subunit	Gallus gallus	238-252
34534897-8	2021	RESULTS: Compared to the control diet, the PR-diet increased serum metabolites related to polyphenols and methylxanthine intake.	methylxanthine	106-120	transmembrane protein 37	Homo sapiens	43-45
35281252-1	2022	The aim of the present study was to test the binding affinity of methylxanthines (caffeine/theine, methylxanthine, theobromine, theophylline and xanthine) to three potential target proteins namely Spike protein (6LZG), main protease (6LU7) and nucleocapsid protein N-terminal RNA binding domain (6M3M) of SARS-CoV-2.	methylxanthine	65-80	surface glycoprotein	Severe acute respiratory syndrome coronavirus 2	197-202
2460096-5	1988	Furthermore, additional methylxanthines and dibutyryl cAMP have similar effects on TNF expression.	methylxanthine	24-39	tumor necrosis factor	Homo sapiens	83-86
2686430-6	1989	With respect to the effect on theophylline metabolism, quinolones inhibit specific cytochrome P-450 isozymes responsible for metabolism of methylxanthines, although there are major differences between the quinolones.	methylxanthine	139-154	cytochrome P450 family 2 subfamily B member 6	Homo sapiens	94-99
2570368-0	1989	Methylxanthines augment the renin response to suprarenal-aortic constriction.	methylxanthine	0-15	renin	Canis lupus familiaris	28-33
2570368-2	1989	The purpose of the present investigation was to determine whether methylxanthines augment the increase in renin secretion induced by a reduction in renal perfusion pressure and, if so, whether this effect is mediated by a direct action on juxtaglomerular cells.	methylxanthine	66-81	renin	Canis lupus familiaris	106-111
2570368-8	1989	These results indicate that methylxanthines can potentiate the renin response to a reduction in renal perfusion pressure most likely by directly affecting the juxtaglomerular cells; however, since increased sodium delivery to the macula densa inhibits renin release, the extent to which methylxanthines affect the renin response to renal artery hypotension depends on how vigorous the diuretic response is to a given methylxanthine.	methylxanthine	28-43	renin	Canis lupus familiaris	63-68
2570368-8	1989	These results indicate that methylxanthines can potentiate the renin response to a reduction in renal perfusion pressure most likely by directly affecting the juxtaglomerular cells; however, since increased sodium delivery to the macula densa inhibits renin release, the extent to which methylxanthines affect the renin response to renal artery hypotension depends on how vigorous the diuretic response is to a given methylxanthine.	methylxanthine	287-302	renin	Canis lupus familiaris	63-68
2570368-8	1989	These results indicate that methylxanthines can potentiate the renin response to a reduction in renal perfusion pressure most likely by directly affecting the juxtaglomerular cells; however, since increased sodium delivery to the macula densa inhibits renin release, the extent to which methylxanthines affect the renin response to renal artery hypotension depends on how vigorous the diuretic response is to a given methylxanthine.	methylxanthine	28-42	renin	Canis lupus familiaris	63-68
2570368-8	1989	These results indicate that methylxanthines can potentiate the renin response to a reduction in renal perfusion pressure most likely by directly affecting the juxtaglomerular cells; however, since increased sodium delivery to the macula densa inhibits renin release, the extent to which methylxanthines affect the renin response to renal artery hypotension depends on how vigorous the diuretic response is to a given methylxanthine.	methylxanthine	28-42	renin	Canis lupus familiaris	252-257
2570368-8	1989	These results indicate that methylxanthines can potentiate the renin response to a reduction in renal perfusion pressure most likely by directly affecting the juxtaglomerular cells; however, since increased sodium delivery to the macula densa inhibits renin release, the extent to which methylxanthines affect the renin response to renal artery hypotension depends on how vigorous the diuretic response is to a given methylxanthine.	methylxanthine	28-42	renin	Canis lupus familiaris	252-257
2897987-1	1988	A possible role of methylxanthines in the high incidence of gastroesophageal reflux (GER) in patients with asthma has been suggested.	methylxanthine	19-34	GER	Homo sapiens	85-88
2840908-10	1988	Our results suggest that the two methylxanthines inhibit both phospholipase A2 and phospholipase C, the former displaying a greater sensitivity to the two drugs.	methylxanthine	33-48	phospholipase A2 group IB	Homo sapiens	62-78
2460096-3	1988	In this study, we present data demonstrating pentoxifylline, a methylxanthine, is efficacious in suppressing LPS-induced MO-derived TNF at the level of both TNF mRNA accumulation and TNF supernatant bioactivity.	methylxanthine	63-77	tumor necrosis factor	Homo sapiens	132-135
3890497-4	1985	This effect is similar to that of the methylxanthines inhibiting phosphodiesterase propitiating the increase of CAMP and favouring bronchodilatation.	methylxanthine	38-53	cathelicidin antimicrobial peptide	Homo sapiens	112-116
2434564-2	1987	The effect of therapeutic concentrations of methylxanthines on human neutrophil functions stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP) was examined.	methylxanthine	44-59	formyl peptide receptor 1	Homo sapiens	145-149
3526315-5	1986	However, as the methylxanthines are potent adenosine receptor antagonists, we suggest that in the human chorion adenosine is a mediator of renin release.	methylxanthine	16-31	renin	Homo sapiens	139-144
2882985-3	1987	It appears that the high affinity enzyme is a polycyclic aromatic hydrocarbon-inducible isozyme of cytochrome P-450, based on competitive inhibition by 7-ethoxyresorufin and benzo[a]pyrene, and based on a significant (p less than 0.001) correlation between 7-ethoxyresorufin-O-deethylation and methylxanthine demethylation rates.	methylxanthine	294-308	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	99-115
3084068-8	1986	The greatest number of aberrations was seen in HN2-treated cells exposed briefly to MEX in late S-G2.	methylxanthine	84-87	MT-RNR2 like 2 (pseudogene)	Homo sapiens	47-50
2991802-5	1985	A role for endogenous adenosine in the modulation of hippocampal noradrenaline release is supported by these findings: (1) that blockade of adenosine receptors by methylxanthines, especially by 8-phenyltheophylline, increased, whereas (2) inhibition of the uptake of adenosine decreased the evoked release of noradrenaline and (3) that deamination of endogenous extracellular adenosine by addition of adenosine deaminase to the medium enhanced the evoked transmitter release.	methylxanthine	163-178	adenosine deaminase	Oryctolagus cuniculus	401-420
6704726-9	1984	We suggest that methylxanthines may modulate the terminal responses both as a K+ channel blocker and by enhancing the release of Ca2+ from a storage site, perhaps in the inner capsular space, whereas dantrolene has the opposite effect.	methylxanthine	16-31	carbonic anhydrase 2	Homo sapiens	129-132
6208014-9	1984	The effects of the methylxanthines in abolishing insulin action probably relates to interference with insulin-dependent intracellular enzymic activity other than cAMP phosphodiesterase.	methylxanthine	19-34	insulin	Homo sapiens	49-56
6208014-9	1984	The effects of the methylxanthines in abolishing insulin action probably relates to interference with insulin-dependent intracellular enzymic activity other than cAMP phosphodiesterase.	methylxanthine	19-34	insulin	Homo sapiens	102-109
6199230-0	1984	Effects of analogues of adenosine and methyl xanthines on insulin sensitivity in soleus muscle of the rat.	methylxanthine	38-54	insulin	Homo sapiens	58-65
6199230-1	1984	The concentration of insulin that produces half-maximal stimulation of glycolysis by stripped soleus muscle preparations is markedly increased by the adenosine analogues, 2-chloroadenosine and N6-phenylisopropyladenosine, but is markedly decreased by the methyl xanthine analogue, 8-phenyltheophylline.	methylxanthine	255-270	insulin	Homo sapiens	21-28
6247005-1	1980	1 The effects of adenosine and various derivatives were examined in the in vitro hippocampal slice preparation from rat.2 The amplitudes of extracellularly recorded field potentials from the CA1 region were depressed by adenosine, and this effect could be antagonized by methylxanthines.	methylxanthine	271-286	carbonic anhydrase 1	Rattus norvegicus	191-194
6571228-0	1983	Antagonism of enkephalin action on acetylcholine release by methylxanthines: lack of a purine link.	methylxanthine	60-75	proenkephalin	Rattus norvegicus	14-24
6129123-12	1982	Ephedrine has now been superseded by the more selective beta 2-adrenoceptor agonist drugs all of which, whether given orally, intravenously or by inhalation, appear to have an additive effect with the methylxanthines.	methylxanthine	201-216	adrenoceptor beta 2	Homo sapiens	56-75
6668464-0	1983	Influence of some common methylxanthines on contractile responses and calcium mobilization of ileal, vas deferens and bladder smooth muscle.	methylxanthine	25-40	arginine vasopressin	Rattus norvegicus	101-104
173803-0	1975	Inhibition of 5"-nucleotidase in rat brain by methylxanthines.	methylxanthine	46-61	5' nucleotidase, ecto	Rattus norvegicus	14-29
176032-1	1976	The ionophore A23187 increased the release of rat growth hormone in the presence of a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine; a second ionophore X537A inhibited growth hormone release induced by the methylxanthine.	methylxanthine	128-142	gonadotropin releasing hormone receptor	Rattus norvegicus	50-64
202467-0	1978	Effect of methylxanthines on binding of the glucocorticoid receptor to DNA-cellulose and nuclei.	methylxanthine	10-25	nuclear receptor subfamily 3, group C, member 1	Rattus norvegicus	44-67
190648-1	1977	The methyl xanthines, theophylline, caffeine and 3-isobutyl-1 methyl xanthine (MIX) inhibited the pressure responses to noradrnealine, angiotensin II and potassium ions in the isolated perfused mesenteric vascular bed of the male rat.	methylxanthine	4-20	angiotensinogen	Rattus norvegicus	135-149
187878-5	1976	We found that methyl xanthines inhibited the activation of glutathione reductase and that glutathione oxidizing agents act as mitotic inhibitors.	methylxanthine	14-30	glutathione reductase	Mus musculus	59-80
30875347-0	2019	Methylxanthine derivatives promote autophagy in gastric cancer cells targeting PTEN.	methylxanthine	0-14	phosphatase and tensin homolog	Homo sapiens	79-83
31827085-3	2019	We employed chemical library screening to identify and optimize methylxanthine derivatives as selective bioavailable PARG inhibitors.	methylxanthine	64-78	poly(ADP-ribose) glycohydrolase	Homo sapiens	117-121
31827085-4	2019	Multiple crystal structures reveal how substituent positions on the methylxanthine core dictate binding modes and inducible-complementarity with a PARG-specific tyrosine clasp and arginine switch, supporting inhibitor specificity and a competitive inhibition mechanism.	methylxanthine	68-82	poly(ADP-ribose) glycohydrolase	Homo sapiens	147-151
30875347-1	2019	Methylxanthine derivatives, such as caffeine and theophylline, enhance cell apoptosis and autophagy and reportedly induce the activity of phosphatase and tensin homologue (PTEN) and inhibit the mammalian target of rapamycin (mTOR).	methylxanthine	0-14	phosphatase and tensin homolog	Homo sapiens	172-176
30875347-1	2019	Methylxanthine derivatives, such as caffeine and theophylline, enhance cell apoptosis and autophagy and reportedly induce the activity of phosphatase and tensin homologue (PTEN) and inhibit the mammalian target of rapamycin (mTOR).	methylxanthine	0-14	mechanistic target of rapamycin kinase	Homo sapiens	194-223
30875347-1	2019	Methylxanthine derivatives, such as caffeine and theophylline, enhance cell apoptosis and autophagy and reportedly induce the activity of phosphatase and tensin homologue (PTEN) and inhibit the mammalian target of rapamycin (mTOR).	methylxanthine	0-14	mechanistic target of rapamycin kinase	Homo sapiens	225-229
30875347-7	2019	PTEN knockdown impaired the methylxanthine derivative-mediated inhibition of PI3K/Akt/mTOR signalling.	methylxanthine	28-42	phosphatase and tensin homolog	Homo sapiens	0-4
30875347-7	2019	PTEN knockdown impaired the methylxanthine derivative-mediated inhibition of PI3K/Akt/mTOR signalling.	methylxanthine	28-42	AKT serine/threonine kinase 1	Homo sapiens	82-85
30875347-7	2019	PTEN knockdown impaired the methylxanthine derivative-mediated inhibition of PI3K/Akt/mTOR signalling.	methylxanthine	28-42	mechanistic target of rapamycin kinase	Homo sapiens	86-90
30875347-9	2019	These results show that the methylxanthine derivatives (caffeine and theophylline) effectively induce gastric cancer cell apoptosis and autophagy by PTEN activation and PI3K/Akt/mTOR pathway suppression and strongly support the use of methylxanthine derivatives as potential anticancer therapeutics.	methylxanthine	28-42	phosphatase and tensin homolog	Homo sapiens	149-153
30875347-9	2019	These results show that the methylxanthine derivatives (caffeine and theophylline) effectively induce gastric cancer cell apoptosis and autophagy by PTEN activation and PI3K/Akt/mTOR pathway suppression and strongly support the use of methylxanthine derivatives as potential anticancer therapeutics.	methylxanthine	28-42	AKT serine/threonine kinase 1	Homo sapiens	174-177
30875347-9	2019	These results show that the methylxanthine derivatives (caffeine and theophylline) effectively induce gastric cancer cell apoptosis and autophagy by PTEN activation and PI3K/Akt/mTOR pathway suppression and strongly support the use of methylxanthine derivatives as potential anticancer therapeutics.	methylxanthine	28-42	mechanistic target of rapamycin kinase	Homo sapiens	178-182
30875347-1	2019	Methylxanthine derivatives, such as caffeine and theophylline, enhance cell apoptosis and autophagy and reportedly induce the activity of phosphatase and tensin homologue (PTEN) and inhibit the mammalian target of rapamycin (mTOR).	methylxanthine	0-14	phosphatase and tensin homolog	Homo sapiens	138-170
31432005-5	2019	Lifespan studies with the wild type, DAF-16 and SKN-1 mutant strains indicated that the methylxanthines-mediated lifespan extension in C. elegans was independent of DAF-16/FOXO and SKN-1.	methylxanthine	88-103	Fork-head domain-containing protein;Forkhead box protein O	Caenorhabditis elegans	37-43
31432005-5	2019	Lifespan studies with the wild type, DAF-16 and SKN-1 mutant strains indicated that the methylxanthines-mediated lifespan extension in C. elegans was independent of DAF-16/FOXO and SKN-1.	methylxanthine	88-103	BZIP domain-containing protein;Protein skinhead-1	Caenorhabditis elegans	48-53
31432005-5	2019	Lifespan studies with the wild type, DAF-16 and SKN-1 mutant strains indicated that the methylxanthines-mediated lifespan extension in C. elegans was independent of DAF-16/FOXO and SKN-1.	methylxanthine	88-103	Fork-head domain-containing protein;Forkhead box protein O	Caenorhabditis elegans	165-171
30242840-13	2019	We showed that NHA2 is a target of Ca2+ /NFAT signalling and is transcriptionally induced by methylxanthine drugs such as caffeine and theophylline, which are contraindicated in ADPKD patients.	methylxanthine	93-107	solute carrier family 9 member B2	Homo sapiens	15-19