PMID-sentid	Pub_year	Sent_text	compound_name	comp_offset	prot_official_name	organism	prot_offset
33879516-14	2021	ICV tofogliflozin increased phosphorylation of AMPK and c-fos expression in the lateral hypothalamus.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	4-17	protein kinase AMP-activated catalytic subunit alpha 2	Rattus norvegicus	47-51
33377253-0	2021	A decrease in plasma glucose levels is required for increased endogenous glucose production with a single administration of an SGLT2 inhibitor tofogliflozin.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	143-156	solute carrier family 5 member 2	Homo sapiens	127-132
33377253-3	2021	We investigate whether these changes are elicited by the decrease in PG levels induced by SGLT2i tofogliflozin.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	97-110	solute carrier family 5 member 2	Homo sapiens	90-95
34029949-0	2021	The sodium-glucose cotransporter-2 inhibitor Tofogliflozin prevents the progression of nonalcoholic steatohepatitis-associated liver tumors in a novel murine model.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	45-58	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	4-34
34029949-6	2021	In this model, sodium glucose cotransporter 2 inhibitor Tofogliflozin prevented the development of NASH-like liver phenotypes and the progression of liver tumors.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	56-69	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	15-45
34029949-7	2021	Tofogliflozin attenuated p21 expression of hepatocytes in non-tumorous lesions in the liver.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	cyclin-dependent kinase inhibitor 1A (P21)	Mus musculus	25-28
33879516-14	2021	ICV tofogliflozin increased phosphorylation of AMPK and c-fos expression in the lateral hypothalamus.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	4-17	Fos proto-oncogene, AP-1 transcription factor subunit	Rattus norvegicus	56-61
32096571-0	2020	Influence of an SGLT2 inhibitor, tofogliflozin, on the resting heart rate in relation to adipose tissue insulin resistance.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	33-46	solute carrier family 5 member 2	Homo sapiens	16-21
32597517-1	2021	AIMS/INTRODUCTION: Tofogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that lowers plasma glucose levels by enhancing urinary glucose excretion.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	19-32	solute carrier family 5 member 2	Homo sapiens	38-68
32597517-1	2021	AIMS/INTRODUCTION: Tofogliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that lowers plasma glucose levels by enhancing urinary glucose excretion.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	19-32	solute carrier family 5 member 2	Homo sapiens	70-75
33397376-1	2021	BACKGROUND: Tofogliflozin, an SGLT2 inhibitor, is associated with favorable metabolic effects, including improved glycemic control and serum lipid profile and decreased body weight, visceral adipose tissue, and blood pressure (BP).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	12-25	solute carrier family 5 member 2	Homo sapiens	30-35
33098615-0	2020	The sodium-glucose cotransporter 2 inhibitor tofogliflozin prevents diabetic kidney disease progression in type 2 diabetic mice.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	45-58	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	4-34
33098615-4	2020	KK-Ay mice were treated with 0.015% tofogliflozin, which is an SGLT2 inhibitor, starting at seven weeks of age for eight weeks.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	36-49	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	63-68
33098615-7	2020	Tofogliflozin treatment enhanced damage in both the glomerular (i.e., enlarged mesangial area, increased foot process effacement rate, and decreased number of WT-1-positive cells) and tubulointerstitial (increased protein levels of KIM-1 and MCP-1, increased number of macrophages, and abnormal mitochondrial morphology) areas.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	hepatitis A virus cellular receptor 1	Mus musculus	232-237
33098615-7	2020	Tofogliflozin treatment enhanced damage in both the glomerular (i.e., enlarged mesangial area, increased foot process effacement rate, and decreased number of WT-1-positive cells) and tubulointerstitial (increased protein levels of KIM-1 and MCP-1, increased number of macrophages, and abnormal mitochondrial morphology) areas.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	mast cell protease 1	Mus musculus	242-247
32314464-7	2020	Fat mass was reduced by tofogliflozin but was increased by glimepiride (by -2.0 +- 1.7 kg and + 1.6 +- 1.6, p = 0.002).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	24-37	FAT atypical cadherin 1	Homo sapiens	0-3
32314464-8	2020	Fat-free mass was also reduced by tofogliflozin and increased by glimepiride (by -1.3 +- 1.3 kg and + 0.9 +- 2.0, p < 0.001).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	34-47	FAT atypical cadherin 1	Homo sapiens	0-3
33063270-9	2020	CONCLUSIONS: Tofogliflozin was more effective and safer than ipragliflozin in reducing glycemic variability and mitigating hypoglycemia risk in patients with T2DM treated with insulin glargine U300.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	13-26	insulin	Homo sapiens	176-183
32707593-0	2020	Effects of Child-Pugh B Cirrhosis on Pharmacokinetics of Tofogliflozin, a New Sodium-Glucose Co-Transporter (SGLT2) Inhibitor.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	57-70	solute carrier family 5 member 2	Homo sapiens	109-114
32707593-1	2020	BACKGROUND: Tofogliflozin is a highly selective sodium-glucose co-transporter 2 (SGLT2) inhibitor.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	12-25	solute carrier family 5 member 2	Homo sapiens	48-79
32707593-1	2020	BACKGROUND: Tofogliflozin is a highly selective sodium-glucose co-transporter 2 (SGLT2) inhibitor.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	12-25	solute carrier family 5 member 2	Homo sapiens	81-86
32096571-0	2020	Influence of an SGLT2 inhibitor, tofogliflozin, on the resting heart rate in relation to adipose tissue insulin resistance.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	33-46	insulin	Homo sapiens	104-111
32096571-1	2020	AIMS: To examine the effects of a sodium-glucose co-transporter 2 (SGLT2) inhibitor, tofogliflozin, on resting heart rate by exploring baseline factors that independently influenced changes in the resting heart rate.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	85-98	solute carrier family 5 member 2	Homo sapiens	34-65
32096571-1	2020	AIMS: To examine the effects of a sodium-glucose co-transporter 2 (SGLT2) inhibitor, tofogliflozin, on resting heart rate by exploring baseline factors that independently influenced changes in the resting heart rate.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	85-98	solute carrier family 5 member 2	Homo sapiens	67-72
32849941-3	2020	The objective of the present study was to evaluate gender difference in the effect of tofogliflozin, one of the SGLT2 inhibitors, on CVD function in patients with diabetes mellitus.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	86-99	solute carrier family 5 member 2	Homo sapiens	112-117
32646498-1	2020	BACKGROUND: This study aimed to investigate the preventive effects of tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD) by monitoring carotid intima-media thickness (IMT).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	70-83	solute carrier family 5 member 2	Homo sapiens	97-127
32646498-1	2020	BACKGROUND: This study aimed to investigate the preventive effects of tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD) by monitoring carotid intima-media thickness (IMT).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	70-83	solute carrier family 5 member 2	Homo sapiens	129-134
32034997-1	2020	AIMS/INTRODUCTION: Tofogliflozin is a potent and highly selective sodium glucose cotransporter 2 inhibitor and is currently used to treat patients with type 2 diabetes mellitus (T2DM).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	19-32	solute carrier family 5 member 2	Homo sapiens	66-96
31210529-0	2019	Efficacy and Safety of Tofogliflozin on 24-h Glucose Profile Based on Continuous Glucose Monitoring: Crossover Study of Sodium-Glucose Cotransporter 2 Inhibitor.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	23-36	solute carrier family 5 member 2	Homo sapiens	120-150
31608549-9	2020	CONCLUSIONS: Lower basal insulin secretion capacity might predict greater initial BHB elevations and max-BHB levels during long-term tofogliflozin therapy.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	133-146	insulin	Homo sapiens	25-32
31979355-4	2020	Tofogliflozin is metabolized and inactivated by five different enzymes CYP2C18, CYP3A4, CYP3A5, CYP4A11, and CYP4F3.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	cytochrome P450 family 2 subfamily C member 18	Homo sapiens	71-78
31979355-4	2020	Tofogliflozin is metabolized and inactivated by five different enzymes CYP2C18, CYP3A4, CYP3A5, CYP4A11, and CYP4F3.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	cytochrome P450 family 3 subfamily A member 4	Homo sapiens	80-86
31979355-4	2020	Tofogliflozin is metabolized and inactivated by five different enzymes CYP2C18, CYP3A4, CYP3A5, CYP4A11, and CYP4F3.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	cytochrome P450 family 3 subfamily A member 5	Homo sapiens	88-94
31979355-4	2020	Tofogliflozin is metabolized and inactivated by five different enzymes CYP2C18, CYP3A4, CYP3A5, CYP4A11, and CYP4F3.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	cytochrome P450 family 4 subfamily A member 11	Homo sapiens	96-103
31979355-4	2020	Tofogliflozin is metabolized and inactivated by five different enzymes CYP2C18, CYP3A4, CYP3A5, CYP4A11, and CYP4F3.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	cytochrome P450 family 4 subfamily F member 3	Homo sapiens	109-115
31638239-0	2019	Suppressive effects of the sodium-glucose cotransporter 2 inhibitor tofogliflozin on colorectal tumorigenesis in diabetic and obese mice.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	68-81	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	27-57
31638239-3	2019	The purpose of the present study was to investigate the effects of tofogliflozin, a sodium-glucose cotransporter 2 inhibitor, on the development of colorectal cancer in diabetic and obese mice.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	67-80	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	84-114
31638239-6	2019	At the end of the study, administration of tofogliflozin was revealed to significantly suppress the development of colorectal neoplastic lesions and beta-catenin accumulated crypts.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	43-56	catenin (cadherin associated protein), beta 1	Mus musculus	149-161
31638239-7	2019	In the tofogliflozin-treated mice, the levels of blood glucose and serum TNF-alpha, as well as mRNA expression of the pro-inflammatory markers in the white adipose tissue, were reduced.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	7-20	tumor necrosis factor	Mus musculus	73-82
31033218-0	2019	Long-term safety and efficacy of the sodium-glucose cotransporter 2 inhibitor, tofogliflozin, added on glucagon-like peptide-1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52-week open-label, multicenter, post-marketing clinical study.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	79-92	solute carrier family 5 member 2	Homo sapiens	37-67
31033218-0	2019	Long-term safety and efficacy of the sodium-glucose cotransporter 2 inhibitor, tofogliflozin, added on glucagon-like peptide-1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52-week open-label, multicenter, post-marketing clinical study.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	79-92	glucagon	Homo sapiens	103-126
31033218-1	2019	AIMS/INTRODUCTION: Tofogliflozin is a potent and highly selective sodium-glucose cotransporter 2 inhibitor that is currently used to treat patients with type 2 diabetes mellitus.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	19-32	solute carrier family 5 member 2	Homo sapiens	66-96
31033218-4	2019	Tofogliflozin 20 mg was orally administered once daily for 52 weeks with GLP-1 receptor agonist.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	glucagon like peptide 1 receptor	Homo sapiens	73-87
31033218-12	2019	With the addition of tofogliflozin to GLP-1 receptor agonist, the subsequent mean (standard deviation) reduction in glycated hemoglobin was -0.6% (1.0%; P < 0.0001).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	21-34	glucagon like peptide 1 receptor	Homo sapiens	38-52
31033218-14	2019	CONCLUSIONS: Tofogliflozin add-on to GLP-1 receptor agonist monotherapy is an effective treatment option with an acceptable safety profile.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	13-26	glucagon like peptide 1 receptor	Homo sapiens	37-51
31325786-4	2019	The structure-activity relationship (SAR) research on this novel series and a comprehensive in vitro and in vivo biological evaluation afforded compound 39 with high in vitro hSGLT2 inhibitory activity (IC50 = 4.5 nM), good pharmacokinetic profiles, and more remarkable efficacy in C57BL/6J mice and Sprague-Dawley rats than marketed drug tofogliflozin.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	339-352	solute carrier family 5 member 2	Homo sapiens	175-181
30811541-0	2019	Attenuation of Weight Loss Through Improved Antilipolytic Effect in Adipose Tissue Via the SGLT2 Inhibitor Tofogliflozin.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	107-120	solute carrier family 5 member 2	Homo sapiens	91-96
32231752-2	2020	Recent clinical data suggest that several sodium glucose transporter-2 (SGLT2) inhibitors are found to reduce cardiovascular disease (CVD) events in elderly diabetic patients, but the effect of tofogliflozin, one of the SGLT2 inhibitors, on CVD is unknown.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	194-207	solute carrier family 5 member 2	Homo sapiens	220-225
32231752-6	2020	Results: Body weight, systolic and diastolic blood pressures significantly decreased, while renin and aldosterone level significantly increased after 1 month of tofogliflozin treatment.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	161-174	renin	Homo sapiens	92-97
31608549-0	2020	Basal insulin secretion capacity predicts the initial response and maximum levels of beta-hydroxybutyrate during therapy with the SGLT2 inhibitor, tofogliflozin, in relation to weight loss.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	147-160	insulin	Homo sapiens	6-13
31608549-0	2020	Basal insulin secretion capacity predicts the initial response and maximum levels of beta-hydroxybutyrate during therapy with the SGLT2 inhibitor, tofogliflozin, in relation to weight loss.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	147-160	solute carrier family 5 member 2	Homo sapiens	130-135
31979355-1	2020	Dapagliflozin, empagliflozin, tofogliflozin, selective inhibitors of sodium-glucose cotransporter 2 (SGLT2), is used clinically to reduce circulation glucose levels in patients with type 2 diabetes mellitus by blocking the reabsorption of glucose by the kidneys.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	30-43	solute carrier family 5 member 2	Homo sapiens	69-99
31979355-1	2020	Dapagliflozin, empagliflozin, tofogliflozin, selective inhibitors of sodium-glucose cotransporter 2 (SGLT2), is used clinically to reduce circulation glucose levels in patients with type 2 diabetes mellitus by blocking the reabsorption of glucose by the kidneys.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	30-43	solute carrier family 5 member 2	Homo sapiens	101-106
31197929-14	2020	CONCLUSIONS: Our interim 12-month data suggest that tofogliflozin could be used safely and effectively in Japanese patients with type 2 diabetes mellitus, as tofogliflozin was well tolerated with low hypoglycemia risk, and significantly improved HbA1c and bodyweight.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	52-65	hemoglobin subunit alpha 1	Homo sapiens	246-250
32134370-7	2020	Canagliflozin, dapagliflozin, empagliflozin, ipragliflozin, luseogliflozin, and tofogliflozin are known to be SGLT-2 inhibitors.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	80-93	solute carrier family 5 member 2	Homo sapiens	110-116
30702214-1	2019	AIMS/INTRODUCTION: The present study analysis was carried out to evaluate the safety and efficacy of tofogliflozin, a sodium-glucose cotransporter 2 inhibitor, in Japanese patients with type 2 diabetes mellitus in real-world clinical practice.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	101-114	solute carrier family 5 member 2	Homo sapiens	118-148
31321581-3	2019	The purpose of this study was to investigate the effect of tofogliflozin, SGLT2 inhibitor, on systolic and diastolic cardiac function in patients with type 2 diabetes mellitus (T2DM).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	59-72	solute carrier family 5 member 2	Homo sapiens	74-79
30145651-7	2018	METHODS: Sodium glucose cotransporter-2 inhibitor, tofogliflozin versus glimepiride, comparative trial in patients with type 2 diabetes on body composition is an ongoing, multicenter, prospective, randomized, open-label, parallel-group trial.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	51-64	solute carrier family 5 member 2	Homo sapiens	9-39
29766812-0	2019	Switching Dipeptidyl Peptidase-4 Inhibitors to Tofogliflozin, a Selective Inhibitor of Sodium-Glucose Cotransporter 2 Improve Arterial Stiffness Evaluated by Cardio-Ankle Vascular Index in Patients with Type 2 Diabetes: A Pilot Study.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	47-60	dipeptidyl peptidase 4	Homo sapiens	10-32
29766812-0	2019	Switching Dipeptidyl Peptidase-4 Inhibitors to Tofogliflozin, a Selective Inhibitor of Sodium-Glucose Cotransporter 2 Improve Arterial Stiffness Evaluated by Cardio-Ankle Vascular Index in Patients with Type 2 Diabetes: A Pilot Study.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	47-60	solute carrier family 5 member 2	Homo sapiens	87-117
29766812-2	2019	However, it remains unclear whether switching DPP-4 inhibitors to tofogliflozin, a selective inhibitor of Sodium-Glucose Cotransporter 2 (SGLT2) improves arterial stiffness in T2DM patients.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	66-79	solute carrier family 5 member 2	Homo sapiens	106-136
29766812-2	2019	However, it remains unclear whether switching DPP-4 inhibitors to tofogliflozin, a selective inhibitor of Sodium-Glucose Cotransporter 2 (SGLT2) improves arterial stiffness in T2DM patients.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	66-79	solute carrier family 5 member 2	Homo sapiens	138-143
29766812-8	2019	CONCLUSION: The present study suggests that switching DPP-4 inhibitors to tofogliflozin ameliorates arterial stiffness in T2DM patients partly via improvement of liver function.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	74-87	dipeptidyl peptidase 4	Homo sapiens	54-59
30627276-1	2019	Background: We investigated the potential mechanism underlying body weight reduction by the sodium glucose cotransporter 2 (SGLT2) inhibitor, tofogliflozin, during treatment and after subsequent washout.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	142-155	solute carrier family 5 member 2	Homo sapiens	92-122
30627276-1	2019	Background: We investigated the potential mechanism underlying body weight reduction by the sodium glucose cotransporter 2 (SGLT2) inhibitor, tofogliflozin, during treatment and after subsequent washout.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	142-155	solute carrier family 5 member 2	Homo sapiens	124-129
30103216-0	2019	Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of Tofogliflozin (A SELECTIVE SGLT2 Inhibitor) in Patients with Type 2 Diabetes Mellitus.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	75-88	solute carrier family 5 member 2	Homo sapiens	102-107
31105148-2	2019	In this study, we investigated the effects of tofogliflozin, an SGLT2 inhibitor, on cardiac hypertrophy and metabolism in hypertensive rats fed a high-fat diet.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	46-59	solute carrier family 5 member 2	Rattus norvegicus	64-69
31105148-7	2019	Tofogliflozin significantly decreased the expression levels of genes related to cardiac hypertrophy (encoding for natriuretic peptides A and B and interleukin-6), and to cardiac fibrosis (encoding for transforming growth factor-beta1 and collagen type IV), in DS rats.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	natriuretic peptide A	Rattus norvegicus	114-142
31105148-7	2019	Tofogliflozin significantly decreased the expression levels of genes related to cardiac hypertrophy (encoding for natriuretic peptides A and B and interleukin-6), and to cardiac fibrosis (encoding for transforming growth factor-beta1 and collagen type IV), in DS rats.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	interleukin 6	Rattus norvegicus	147-160
31105148-7	2019	Tofogliflozin significantly decreased the expression levels of genes related to cardiac hypertrophy (encoding for natriuretic peptides A and B and interleukin-6), and to cardiac fibrosis (encoding for transforming growth factor-beta1 and collagen type IV), in DS rats.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	transforming growth factor, beta 1	Rattus norvegicus	201-233
30835599-3	2019	Areas covered: Tofogliflozin is the most selective SGLT-2 inhibitor and has been approved for the treatment of T2D in Japan.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	15-28	solute carrier family 5 member 2	Homo sapiens	51-57
30835599-6	2019	However, the clinical data on Tofogliflozin from both clinical and real-world studies remain sparse and much less abundant than the other main 3 SGLT-2 inhibitors, thus calling for caution and underscoring the need for further research.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	30-43	solute carrier family 5 member 2	Homo sapiens	145-151
30682139-2	2019	In this study, we examined whether the development of chronic inflammation and senescence-associated T cells in VAT of DIO mice was improved by long-term weight loss after switching to normal chow (NC) or by administration of a sodium glucose cotransporter 2 inhibitor (tofogliflozin).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	270-283	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	228-258
29660244-0	2018	Unaccounted for regression to the mean renders conclusion of article titled "Uric acid lowering in relation to HbA1c reductions with the SGLT2 inhibitor tofogliflozin" unsubstantiated.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	153-166	solute carrier family 5 member 2	Homo sapiens	137-142
29032638-0	2018	Sodium-glucose cotransporter 2 inhibitor, tofogliflozin, shows better improvements of blood glucose and insulin secretion in patients with high insulin levels at baseline.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	42-55	solute carrier family 5 member 2	Homo sapiens	0-30
29749099-1	2018	titled "Unaccounted for regression to the mean renders conclusion of article titled "Uric acid lowering in relation to HbA1c reductions with the SGLT2 inhibitor Tofogliflozin" unsubstantiated".	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	161-174	solute carrier family 5 member 2	Homo sapiens	145-150
29032638-0	2018	Sodium-glucose cotransporter 2 inhibitor, tofogliflozin, shows better improvements of blood glucose and insulin secretion in patients with high insulin levels at baseline.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	42-55	insulin	Homo sapiens	104-111
29032638-8	2018	DISCUSSION: Although tofogliflozin was effective regardless of baseline insulin level, it showed the highest efficacy in the H group.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	21-34	insulin	Homo sapiens	72-79
29171930-0	2018	Uric acid lowering in relation to HbA1c reductions with the SGLT2 inhibitor tofogliflozin.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	76-89	solute carrier family 5 member 2	Homo sapiens	60-65
29316197-0	2018	Tofogliflozin decreases body fat mass and improves peripheral insulin resistance.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	insulin	Homo sapiens	62-69
29316197-7	2018	Tofogliflozin significantly improved insulin sensitivity and peripheral glucose uptake in patients with T2DM.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	insulin	Homo sapiens	37-44
29316236-9	2018	CONCLUSIONS: This study demonstrates the safety and efficacy of tofogliflozin as add-on to insulin therapy in type 2 diabetes mellitus patients, offering a new therapeutic solution to diabetes management.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	64-77	insulin	Homo sapiens	91-98
29171930-1	2018	An integrated analysis was performed with data from 4 phase 2 and phase 3 studies of tofogliflozin in which patients with type 2 diabetes mellitus received the sodium-glucose cotransporter 2 inhibitor tofogliflozin for up to 24 weeks.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	201-214	solute carrier family 5 member 2	Homo sapiens	160-190
29335890-8	2018	Immediately after the addition of tofogliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, the patient"s HbA1c decreased dramatically with only about an additional 3% BW reduction.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	34-47	solute carrier family 5 member 2	Homo sapiens	51-81
30815551-2	2018	We investigated the effect of the SGLT2 inhibitor, tofogliflozin (TOFO) on renal tubular indices, according to the degree of albuminuria, in type 2 diabetes mellitus (T2DM) patients with preserved renal function.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	66-70	solute carrier family 5 member 2	Homo sapiens	34-39
29520981-11	2018	Consistent with the downregulation of stearoyl-CoA desaturase 1, the ratio of plasma monounsaturated to saturated fatty acids was significantly reduced in the LC with Tofo and in the SR alone groups, but was not altered in the NC with Tofo group.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	167-171	stearoyl-Coenzyme A desaturase 1	Mus musculus	38-63
28846182-4	2018	Any of the SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin, tofogliflozin, luseogliflozin or ipragliflozin) significantly decreased SUA levels compared with control (total weighted mean difference [WMD] -37.73 mumol/L, 95% CI [-40.51, -34.95]).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	74-87	solute carrier family 5 member 2	Homo sapiens	11-16
29335890-8	2018	Immediately after the addition of tofogliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, the patient"s HbA1c decreased dramatically with only about an additional 3% BW reduction.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	34-47	solute carrier family 5 member 2	Homo sapiens	83-88
29507863-1	2018	Sodium-glucose cotransporter 2 inhibitor tofogliflozin is a new type of antidiabetic drug for individuals with type 2 diabetes mellitus (T2DM).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	41-54	solute carrier family 5 member 2	Homo sapiens	0-30
28928093-5	2017	Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0.015% tofogliflozin (TOFO), a highly selective SGLT2 inhibitor, for 3 weeks.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	131-144	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	172-177
28928093-5	2017	Diet-induced obese mice were subjected to hepatic vagotomy (HVx) or sham operation and loaded with high fat diet containing 0.015% tofogliflozin (TOFO), a highly selective SGLT2 inhibitor, for 3 weeks.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	146-150	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	172-177
28864997-2	2017	The aim of the ongoing study described herein is to investigate the preventive effects of tofogliflozin, a potent and selective SGLT2 inhibitor, on the progression of atherosclerosis in subjects with type 2 diabetes (T2DM) using carotid intima-media thickness (IMT), an established marker of cardiovascular disease (CVD), as a marker.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	90-103	solute carrier family 5 member 2	Homo sapiens	128-133
28371205-0	2017	Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J-STEP/INS): Results of a 16-week randomized, double-blind, placebo-controlled multicentre trial.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	23-36	insulin	Homo sapiens	125-132
28371205-1	2017	AIMS: To assess the effects of 16 weeks of tofogliflozin (sodium-glucose co-transporter-2 [SGLT2] inhibitor) treatment vs placebo on glycated haemoglobin (HbA1c) levels in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with insulin monotherapy or insulin plus a dipeptidyl peptidase-4 (DPP-4) inhibitor.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	43-56	solute carrier family 5 member 2	Homo sapiens	58-89
28371205-1	2017	AIMS: To assess the effects of 16 weeks of tofogliflozin (sodium-glucose co-transporter-2 [SGLT2] inhibitor) treatment vs placebo on glycated haemoglobin (HbA1c) levels in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with insulin monotherapy or insulin plus a dipeptidyl peptidase-4 (DPP-4) inhibitor.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	43-56	solute carrier family 5 member 2	Homo sapiens	91-96
28371205-10	2017	CONCLUSIONS: This 16-week double-blind study indicated that, in patients with T2DM whose HbA1c levels were poorly controlled with insulin monotherapy or insulin plus a DPP-4 inhibitor, addition of tofogliflozin was an effective treatment option with an acceptable safety profile.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	197-210	insulin	Homo sapiens	130-137
28371205-10	2017	CONCLUSIONS: This 16-week double-blind study indicated that, in patients with T2DM whose HbA1c levels were poorly controlled with insulin monotherapy or insulin plus a DPP-4 inhibitor, addition of tofogliflozin was an effective treatment option with an acceptable safety profile.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	197-210	dipeptidyl peptidase 4	Homo sapiens	168-173
27304784-1	2016	Tofogliflozin is a novel selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) and has been developed for the treatment of patients with type 2 diabetes mellitus.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	91-96
28938561-0	2017	Preventive effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on diethylnitrosamine-induced liver tumorigenesis in obese and diabetic mice.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	67-80	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	26-56
28938561-2	2017	In this study, we investigated the effects of the sodium glucose cotransporter 2 inhibitor tofogliflozin on the development of non-alcoholic fatty liver disease-related liver tumorigenesis in C57BL/KsJ-+Lepr db /+Lepr db obese and diabetic mice.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	91-104	leptin receptor	Mus musculus	203-207
27738482-16	2016	CONCLUSIONS: Tofogliflozin may offer a new option for patients whose T2DM remains inadequately controlled on insulin therapy with or without additional oral glucose-lowering agents.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	13-26	insulin	Homo sapiens	109-116
27304784-1	2016	Tofogliflozin is a novel selective inhibitor of sodium-dependent glucose co-transporter-2 (SGLT2) and has been developed for the treatment of patients with type 2 diabetes mellitus.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	48-89
28427104-0	2017	Pharmacokinetics and Pharmacodynamics of Tofogliflozin (a Selective SGLT2 Inhibitor) in Healthy Male Subjects.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	41-54	solute carrier family 5 member 2	Homo sapiens	68-73
28427104-4	2017	Tofogliflozin was absorbed rapidly and eliminated from the systemic circulation with a t1/2 of 5-6 h. Exposure increased dose-proportionally up to 320 mg.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	CD5 molecule	Homo sapiens	87-98
30279791-6	2017	Tofogliflozin, a SGLT2 inhibitor, successfully increased urine volume, and reduced body weight, HbA1c, and urinary protein excretion (10.8 to 2.6 g/day) during 24 weeks.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	17-22
30603323-2	2017	We previously reported that administration of tofogliflozin, a sodium glucose cotransporter 2 inhibitor, for 8 weeks decreased fat-free mass without affecting fat mass.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	46-59	solute carrier family 5 member 2	Homo sapiens	63-93
27407083-0	2016	Tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2, suppresses renal damage in KKAy/Ta mice, obese and type 2 diabetic animals.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	40-70
27407083-3	2016	We examined whether tofogliflozin, an inhibitor of sodium-glucose cotransporter 2, suppressed renal damage in KKAy/Ta mice, obese and type 2 diabetic animals.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	20-33	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	51-81
26871504-1	2016	An efficient and scalable synthesis of an antidiabetic drug, tofogliflozin (1), which was identified as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor, is described.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	61-74	solute carrier family 5 member 2	Homo sapiens	123-153
26871504-1	2016	An efficient and scalable synthesis of an antidiabetic drug, tofogliflozin (1), which was identified as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor, is described.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	61-74	solute carrier family 5 member 2	Homo sapiens	155-160
26158794-0	2016	A Pharmacokinetic/Pharmacodynamic Drug-Drug Interaction Study of Tofogliflozin (a New SGLT2 Inhibitor) and Selected Anti-Type 2 Diabetes Mellitus Drugs.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	65-78	solute carrier family 5 member 2	Homo sapiens	86-91
26158396-0	2016	Tofogliflozin, A Highly Selective Inhibitor of SGLT2 Blocks Proinflammatory and Proapoptotic Effects of Glucose Overload on Proximal Tubular Cells Partly by Suppressing Oxidative Stress Generation.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	47-52
26158396-8	2016	Monocyte chemoattractant protein-1 (MCP-1) gene expression and apoptotic cell death were induced by 4 h- and 8 day-exposure to high glucose, respectively, both of which were also blocked by tofogliflozin or NAC.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	190-203	chemokine (C-C motif) ligand 2	Mus musculus	0-34
26158396-8	2016	Monocyte chemoattractant protein-1 (MCP-1) gene expression and apoptotic cell death were induced by 4 h- and 8 day-exposure to high glucose, respectively, both of which were also blocked by tofogliflozin or NAC.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	190-203	chemokine (C-C motif) ligand 2	Mus musculus	36-41
26158794-1	2016	OBJECTIVE: Tofogliflozin is an oral hypoglycemic agent with a novel mechanism of action that reduces blood glucose levels by promoting glucose excretion in urine, achieved by selectively inhibiting sodium-glucose co-transporter 2 (SGLT2).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	11-24	solute carrier family 5 member 2	Homo sapiens	198-229
26158794-1	2016	OBJECTIVE: Tofogliflozin is an oral hypoglycemic agent with a novel mechanism of action that reduces blood glucose levels by promoting glucose excretion in urine, achieved by selectively inhibiting sodium-glucose co-transporter 2 (SGLT2).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	11-24	solute carrier family 5 member 2	Homo sapiens	231-236
26179482-0	2015	A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	64-77	solute carrier family 5 member 2	Homo sapiens	22-52
27803439-0	2016	Pharmacological analysis of SGLT2 inhibitor (tofogliflozin) using in vivo glucose clamp and titration protocols in rats and cynomolgus monkeys.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	45-58	solute carrier family 5 member 2	Rattus norvegicus	28-33
26179482-1	2015	AIM: To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	75-88	solute carrier family 5 member 2	Homo sapiens	116-146
26179482-1	2015	AIM: To assess the efficacy, safety and tolerability of different doses of tofogliflozin, a novel, highly selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes mellitus (T2DM).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	75-88	solute carrier family 5 member 2	Homo sapiens	148-153
25805666-4	2015	Several SGLT2 inhibitors are already available in many countries (dapagliflozin, canagliflozin, empagliflozin) and in Japan (ipragliflozin, tofogliflozin).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	140-153	solute carrier family 5 member 2	Homo sapiens	8-13
25525634-0	2014	Tofogliflozin: a highly selective SGLT2 inhibitor for the treatment of type 2 diabetes.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	34-39
25350082-0	2015	In vitro profiling of the metabolism and drug-drug interaction of tofogliflozin, a potent and highly specific sodium-glucose co-transporter 2 inhibitor, using human liver microsomes, human hepatocytes, and recombinant human CYP.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	66-79	peptidylprolyl isomerase G	Homo sapiens	224-227
25350082-5	2015	The metabolic pathway of tofogliflozin to M1 was considered to be as follows: first, tofogliflozin was catalyzed to the primary hydroxylated derivative (M4) by CYP2C18, CYP4A11 and CYP4F3B, then M4 was oxidized to M1.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	25-38	cytochrome P450 family 2 subfamily C member 18	Homo sapiens	160-167
25350082-5	2015	The metabolic pathway of tofogliflozin to M1 was considered to be as follows: first, tofogliflozin was catalyzed to the primary hydroxylated derivative (M4) by CYP2C18, CYP4A11 and CYP4F3B, then M4 was oxidized to M1.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	25-38	cytochrome P450 family 4 subfamily A member 11	Homo sapiens	169-176
25350082-5	2015	The metabolic pathway of tofogliflozin to M1 was considered to be as follows: first, tofogliflozin was catalyzed to the primary hydroxylated derivative (M4) by CYP2C18, CYP4A11 and CYP4F3B, then M4 was oxidized to M1.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	85-98	cytochrome P450 family 2 subfamily C member 18	Homo sapiens	160-167
25350082-5	2015	The metabolic pathway of tofogliflozin to M1 was considered to be as follows: first, tofogliflozin was catalyzed to the primary hydroxylated derivative (M4) by CYP2C18, CYP4A11 and CYP4F3B, then M4 was oxidized to M1.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	85-98	cytochrome P450 family 4 subfamily A member 11	Homo sapiens	169-176
25525634-4	2014	Tofogliflozin is the most selective SGLT2 inhibitor, with HbA1c reductions ranging from -0.44% to -0.99% throughout clinical studies, and it is well tolerated with a low rate of drug-related adverse events.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	36-41
24761001-0	2014	Competitive inhibition of SGLT2 by tofogliflozin or phlorizin induces urinary glucose excretion through extending splay in cynomolgus monkeys.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	35-48	solute carrier family 5 member 2	Homo sapiens	26-31
25352807-7	2014	The model shows that concentration levels of tofogliflozin, ipragliflozin, and empagliflozin are higher than levels of other inhibitors following administration of marketed SGLT2 inhibitors at labeled doses and non-marketed SGLT2 inhibitors at maximal doses (approved for phase 2/3 studies).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	45-58	solute carrier family 5 member 2	Homo sapiens	173-178
25352807-7	2014	The model shows that concentration levels of tofogliflozin, ipragliflozin, and empagliflozin are higher than levels of other inhibitors following administration of marketed SGLT2 inhibitors at labeled doses and non-marketed SGLT2 inhibitors at maximal doses (approved for phase 2/3 studies).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	45-58	solute carrier family 5 member 2	Homo sapiens	224-229
25000147-0	2014	Tofogliflozin, a sodium/glucose cotransporter 2 inhibitor, attenuates body weight gain and fat accumulation in diabetic and obese animal models.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	17-47
25000147-1	2014	OBJECTIVE: Tofogliflozin, a highly selective inhibitor of sodium/glucose cotransporter 2 (SGLT2), induces urinary glucose excretion (UGE), improves hyperglycemia and reduces body weight in patients with Type 2 diabetes (T2D).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	11-24	solute carrier family 5 member 2	Homo sapiens	58-88
25000147-1	2014	OBJECTIVE: Tofogliflozin, a highly selective inhibitor of sodium/glucose cotransporter 2 (SGLT2), induces urinary glucose excretion (UGE), improves hyperglycemia and reduces body weight in patients with Type 2 diabetes (T2D).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	11-24	solute carrier family 5 member 2	Homo sapiens	90-95
24761001-4	2014	In cells overexpressing cynomolgus monkey SGLT2 (cSGLT2), both tofogliflozin and phlorizin competitively inhibited uptake of the substrate (alpha-methyl-d-glucopyranoside; AMG).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	63-76	solute carrier family 5 member 2	Homo sapiens	42-47
22410641-4	2012	The selectivity of tofogliflozin toward human SGLT2 versus human SGLT1, SGLT6, and sodium/myo-inositol transporter 1 was the highest among the tested SGLT2 inhibitors under clinical development.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	19-32	solute carrier family 5 member 11	Homo sapiens	72-77
24787286-4	2014	Tofogliflozin is a further SGLT-2 inhibitor, which exhibits the highest selectivity for SGLT-2, the most potent antidiabetic action and a reduced risk of hypoglycaemia.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	27-33
24787286-4	2014	Tofogliflozin is a further SGLT-2 inhibitor, which exhibits the highest selectivity for SGLT-2, the most potent antidiabetic action and a reduced risk of hypoglycaemia.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	88-94
24074237-0	2014	Metabolism and mass balance of SGLT2 inhibitor tofogliflozin following oral administration to humans.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	47-60	solute carrier family 5 member 2	Homo sapiens	31-36
24074237-2	2014	Tofogliflozin is a novel and selective SGLT2 inhibitor increasing glucosuria by inhibition of glucose re-absorption in the kidney for the treatment of type 2 diabetes mellitus.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	39-44
23249697-0	2013	Selective SGLT2 inhibition by tofogliflozin reduces renal glucose reabsorption under hyperglycemic but not under hypo- or euglycemic conditions in rats.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	30-43	solute carrier family 5 member 2	Rattus norvegicus	10-15
24848755-1	2014	Tofogliflozin (Apleway( ), Deberza( ) [Japan]), an orally active small molecule sodium-glucose co-transporter type 2 (SGLT2) inhibitor, has been developed by Chugai Pharmaceutical for the treatment of type 2 diabetes mellitus (T2DM), and a marketing authorization application was filed in Japan in 2013 by licensees Sanofi K.K.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	80-116
24848755-1	2014	Tofogliflozin (Apleway( ), Deberza( ) [Japan]), an orally active small molecule sodium-glucose co-transporter type 2 (SGLT2) inhibitor, has been developed by Chugai Pharmaceutical for the treatment of type 2 diabetes mellitus (T2DM), and a marketing authorization application was filed in Japan in 2013 by licensees Sanofi K.K.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	118-123
24512053-0	2014	Long-term safety and efficacy of tofogliflozin, a selective inhibitor of sodium-glucose cotransporter 2, as monotherapy or in combination with other oral antidiabetic agents in Japanese patients with type 2 diabetes mellitus: multicenter, open-label, randomized controlled trials.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	33-46	solute carrier family 5 member 2	Homo sapiens	73-103
24678906-0	2014	Efficacy and safety of monotherapy with the novel sodium/glucose cotransporter-2 inhibitor tofogliflozin in Japanese patients with type 2 diabetes mellitus: a combined Phase 2 and 3 randomized, placebo-controlled, double-blind, parallel-group comparative study.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	91-104	solute carrier family 5 member 2	Homo sapiens	50-80
24678906-3	2014	We report the results of a combined Phase 2 and 3 clinical study (Japic CTI-101349) of the SGLT2 inhibitor tofogliflozin (CSG452, RG7201) in Japanese patients with type 2 diabetes mellitus.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	107-120	solute carrier family 5 member 2	Homo sapiens	91-96
23751087-0	2013	Tofogliflozin, a novel sodium-glucose co-transporter 2 inhibitor, improves renal and pancreatic function in db/db mice.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	23-54
23751087-9	2013	CONCLUSIONS AND IMPLICATIONS: Long-term inhibition of renal SGLT2 by tofogliflozin not only preserved pancreatic beta-cell function, but also prevented kidney dysfunction in a mouse model of type 2 diabetes.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	69-82	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	60-65
22889351-0	2012	Discovery of tofogliflozin, a novel C-arylglucoside with an O-spiroketal ring system, as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	13-26	solute carrier family 5 member 2	Homo sapiens	108-138
22889351-0	2012	Discovery of tofogliflozin, a novel C-arylglucoside with an O-spiroketal ring system, as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	13-26	solute carrier family 5 member 2	Homo sapiens	140-145
22410641-0	2012	Tofogliflozin, a potent and highly specific sodium/glucose cotransporter 2 inhibitor, improves glycemic control in diabetic rats and mice.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Rattus norvegicus	44-74
22410641-2	2012	We identified a novel potent and selective SGLT2 inhibitor, tofogliflozin (CSG452), and examined its efficacy and pharmacological properties as an antidiabetic drug.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	60-73	solute carrier family 5 member 2	Rattus norvegicus	43-48
22410641-3	2012	Tofogliflozin competitively inhibited SGLT2 in cells overexpressing SGLT2, and K(i) values for human, rat, and mouse SGLT2 inhibition were 2.9, 14.9, and 6.4 nM, respectively.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	38-43
22410641-3	2012	Tofogliflozin competitively inhibited SGLT2 in cells overexpressing SGLT2, and K(i) values for human, rat, and mouse SGLT2 inhibition were 2.9, 14.9, and 6.4 nM, respectively.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 member 2	Homo sapiens	68-73
22410641-3	2012	Tofogliflozin competitively inhibited SGLT2 in cells overexpressing SGLT2, and K(i) values for human, rat, and mouse SGLT2 inhibition were 2.9, 14.9, and 6.4 nM, respectively.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	68-73
22410641-4	2012	The selectivity of tofogliflozin toward human SGLT2 versus human SGLT1, SGLT6, and sodium/myo-inositol transporter 1 was the highest among the tested SGLT2 inhibitors under clinical development.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	19-32	solute carrier family 5 member 2	Homo sapiens	46-51
22410641-4	2012	The selectivity of tofogliflozin toward human SGLT2 versus human SGLT1, SGLT6, and sodium/myo-inositol transporter 1 was the highest among the tested SGLT2 inhibitors under clinical development.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	19-32	solute carrier family 5 member 1	Homo sapiens	65-70
22410641-4	2012	The selectivity of tofogliflozin toward human SGLT2 versus human SGLT1, SGLT6, and sodium/myo-inositol transporter 1 was the highest among the tested SGLT2 inhibitors under clinical development.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	19-32	solute carrier family 5 member 3	Homo sapiens	83-116
22410641-4	2012	The selectivity of tofogliflozin toward human SGLT2 versus human SGLT1, SGLT6, and sodium/myo-inositol transporter 1 was the highest among the tested SGLT2 inhibitors under clinical development.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	19-32	solute carrier family 5 member 2	Homo sapiens	150-155
22410641-10	2012	These findings demonstrate that tofogliflozin inhibits SGLT2 in a specific manner, lowers blood glucose levels by increasing renal glucose clearance, and improves pathological conditions of type 2 diabetes with a low hypoglycemic potential.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	32-45	solute carrier family 5 member 2	Rattus norvegicus	55-60
33764804-2	2021	Here, we tested whether a glucose cotransporter 2 inhibitor (SGLT2-i; tofogliflozin) increased this PVAT effect to prevent the deterioration of cardiac function in aging SHRSP.ZF rats.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	70-83	solute carrier family 5 member 2	Rattus norvegicus	61-66
34617381-4	2022	All of the included SGLT-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin, ipragliflozin, luseogliflozin and tofogliflozin) significantly decreased SUA levels compared with those of the control (total standard mean difference (SMD) -0.965, 95% CI (-1.029, -0.901), P = 0.000, I2  = 98.7%) in patients with T2DM.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	118-131	solute carrier family 5 member 2	Homo sapiens	20-26
33769665-0	2021	Association of estimated plasma volume and weight loss after long-term administration and subsequent discontinuation of the SGLT2 inhibitor, tofogliflozin.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	141-154	solute carrier family 5 member 2	Homo sapiens	124-129
33769665-8	2021	Two weeks after discontinuation of tofogliflozin, BW, ePV and ln-BNP were significantly increased.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	35-48	natriuretic peptide B	Homo sapiens	65-68
34216511-0	2022	Successful Withdrawal of Erythropoiesis-stimulating Agent after Administration of an SGLT2 Inhibitor, Tofogliflozin, in People with Diabetes.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	102-115	solute carrier family 5 member 2	Homo sapiens	85-90
34843041-0	2021	The effect of sodium-glucose cotransporter 2 inhibitor (tofogliflozin) on renal tubular damage in diabetic patients without albuminuria.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	56-69	solute carrier family 5 member 2	Homo sapiens	14-44
34843041-5	2021	METHODS: The SGLT2 inhibitor tofogliflozin (20 mg, 1 x /day) was orally administered to 14 non-albuminuric diabetic patients.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	29-42	solute carrier family 5 member 2	Homo sapiens	13-18
34843041-9	2021	RESULTS: Compared to baseline, the patients" HbA1c values and body weights were significantly decreased post-tofogliflozin administration, and their eGFR values were decreased at 3 months but recovered at 6 months; the hemoglobin concentrations were significantly increased at 3 and 6 months and the urinary NGAL level tended to be decreased at 3 months.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	109-122	lipocalin 2	Homo sapiens	308-312
34388297-1	2021	AIM: To investigate acute effects of add-on therapy with the sodium glucose co-transporter 2 inhibitor tofogliflozin to dipeptidyl peptidase (DPP)-4 inhibitors on 24-hour glucose profile and glycemic variability evaluated by continuous glucose monitoring (CGM) in patients with type 2 diabetes.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	103-116	solute carrier family 5 member 2	Homo sapiens	61-92
34766565-0	2021	Effects of tofogliflozin on adrenocorticotropic hormone, renin and aldosterone, and cortisol levels in elderly patients with diabetes mellitus: A retrospective study of a patient cohort.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	11-24	proopiomelanocortin	Homo sapiens	28-55
34766565-0	2021	Effects of tofogliflozin on adrenocorticotropic hormone, renin and aldosterone, and cortisol levels in elderly patients with diabetes mellitus: A retrospective study of a patient cohort.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	11-24	renin	Homo sapiens	57-62
34766565-2	2021	We retrospectively investigated the effect of tofogliflozin on serum ACTH and cortisol levels in elderly patients with T2DM.Patients received 20 mg tofogliflozin daily for 3 months.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	46-59	proopiomelanocortin	Homo sapiens	69-73
34766565-3	2021	Serum ACTH and cortisol levels were measured at baseline, as well as after 1 month and 3 months of tofogliflozin therapy.Serum ACTH levels were significantly reduced 3 months after tofogliflozin treatment (P < .01).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	99-112	proopiomelanocortin	Homo sapiens	6-10
34766565-3	2021	Serum ACTH and cortisol levels were measured at baseline, as well as after 1 month and 3 months of tofogliflozin therapy.Serum ACTH levels were significantly reduced 3 months after tofogliflozin treatment (P < .01).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	99-112	proopiomelanocortin	Homo sapiens	127-131
34766565-3	2021	Serum ACTH and cortisol levels were measured at baseline, as well as after 1 month and 3 months of tofogliflozin therapy.Serum ACTH levels were significantly reduced 3 months after tofogliflozin treatment (P < .01).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	181-194	proopiomelanocortin	Homo sapiens	6-10
34766565-3	2021	Serum ACTH and cortisol levels were measured at baseline, as well as after 1 month and 3 months of tofogliflozin therapy.Serum ACTH levels were significantly reduced 3 months after tofogliflozin treatment (P < .01).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	181-194	proopiomelanocortin	Homo sapiens	127-131
34766565-6	2021	Renin levels were significantly increased 1 month after treatment (P < .05), maintaining serum aldosterone levels in parallel with the extracellular fluid.Our findings suggested that tofogliflozin decreased both serum ACTH and cortisol levels, with higher levels observed in the high BMI group.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	183-196	renin	Homo sapiens	0-5
34766565-6	2021	Renin levels were significantly increased 1 month after treatment (P < .05), maintaining serum aldosterone levels in parallel with the extracellular fluid.Our findings suggested that tofogliflozin decreased both serum ACTH and cortisol levels, with higher levels observed in the high BMI group.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	183-196	proopiomelanocortin	Homo sapiens	218-222
34766565-7	2021	Tofogliflozin increased serum renin levels while maintaining serum aldosterone and extracellular fluid levels.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	renin	Homo sapiens	30-35
34388297-1	2021	AIM: To investigate acute effects of add-on therapy with the sodium glucose co-transporter 2 inhibitor tofogliflozin to dipeptidyl peptidase (DPP)-4 inhibitors on 24-hour glucose profile and glycemic variability evaluated by continuous glucose monitoring (CGM) in patients with type 2 diabetes.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	103-116	dipeptidyl peptidase 4	Homo sapiens	120-148
34388297-9	2021	CONCLUSIONS: Add-on therapy with tofogliflozin to DPP-4 inhibitors acutely reduces 24-hour glucose levels and improves glycemic variability in patients with type 2 diabetes.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	33-46	dipeptidyl peptidase 4	Homo sapiens	50-55
34603858-4	2021	We reviewed 127 articles and analyses of randomized controlled trials using several drugs in the SGLT2 inhibitor family (sotagliflozin, canagliflozin, dapagliflozin, tofogliflozin) over the past five years, out of which 58 met the criteria and aim of the study.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	166-179	solute carrier family 5 member 2	Homo sapiens	97-102
34357559-2	2021	We evaluated the influence of a sodium-glucose cotransporter 2 (SGLT2) inhibitor, tofogliflozin, on treatment-related QOL in Japanese patients with type 2 diabetes mellitus (T2DM).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	82-95	solute carrier family 5 member 2	Homo sapiens	32-62
34357559-2	2021	We evaluated the influence of a sodium-glucose cotransporter 2 (SGLT2) inhibitor, tofogliflozin, on treatment-related QOL in Japanese patients with type 2 diabetes mellitus (T2DM).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	82-95	solute carrier family 5 member 2	Homo sapiens	64-69
34357559-7	2021	Tofogliflozin treatment increased the total score of DTR-QOL7 from baseline (P < 0.001), while conventional treatment did not change it.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	protein phosphatase 1 regulatory subunit 42	Homo sapiens	53-61
35367765-4	2022	Two kinds of SGLT2 inhibitors, Luseogliflozin and Tofogliflozin substantially suppressed the proliferation of MT-1 and MT-2 cells in both adherent and anchorage-independent culture conditions.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	50-63	solute carrier family 5 member 2	Homo sapiens	13-18
35203369-0	2022	Selective PPARalpha Modulator Pemafibrate and Sodium-Glucose Cotransporter 2 Inhibitor Tofogliflozin Combination Treatment Improved Histopathology in Experimental Mice Model of Non-Alcoholic Steatohepatitis.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	87-100	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	46-76
35203369-2	2022	In this study, we evaluated the effect of the selective PPARalpha modulator (SPPARMalpha) pemafibrate (Pema) and sodium-glucose cotransporter 2 (SGLT2) inhibitor tofogliflozin (Tofo) combination treatment on pathological progression in the liver of a mouse model of NASH (STAM) at two time points (onset of NASH progression and HCC survival).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	162-175	solute carrier family 5 (sodium/glucose cotransporter), member 2	Mus musculus	145-150
35203369-5	2022	RNA-seq analysis suggested that Pema and Tofo combination treatment resulted in an increase in glyceroneogenesis, triglyceride (TG) uptake, lipolysis and liberated fatty acids re-esterification into TG, lipid droplet (LD) formation, and Cidea/Cidec ratio along with an increased number and reduced size and area of LDs.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	41-45	cell death-inducing DNA fragmentation factor, alpha subunit-like effector A	Mus musculus	237-242
35203369-5	2022	RNA-seq analysis suggested that Pema and Tofo combination treatment resulted in an increase in glyceroneogenesis, triglyceride (TG) uptake, lipolysis and liberated fatty acids re-esterification into TG, lipid droplet (LD) formation, and Cidea/Cidec ratio along with an increased number and reduced size and area of LDs.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	41-45	cell death-inducing DFFA-like effector c	Mus musculus	243-248
35280867-14	2022	Tofogliflozin and pioglitazone induced a significantly higher decrease in the K-18 level than a placebo.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	keratin 18	Homo sapiens	78-82
35280867-19	2022	Semaglutide was obviously superior to empagliflozin, liraglutide, dulaglutide, and tofogliflozin in decreasing the AST level.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	83-96	solute carrier family 17 member 5	Homo sapiens	115-118
35280867-22	2022	Tofogliflozin and pioglitazone induced a significantly higher decrease in the K-18 level than dulaglutide.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	keratin 18	Homo sapiens	78-82
35280867-26	2022	Tofogliflozin treatment had the highest SUCRA ranking in decreasing K-18, while dapagliflozin treatment had the highest SUCRA ranking in decreasing the GGT level.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	0-13	keratin 18	Homo sapiens	68-72
35123483-3	2022	This study aimed to evaluate the effects of tofogliflozin, a selective SGLT2 inhibitor, on the tissue characteristics of the human arterial wall in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD).	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	44-57	solute carrier family 5 member 2	Homo sapiens	71-76
35163285-8	2022	The systemic tofogliflozin treatment prevented the activation of glial fibrillary acidic protein and VEGF protein expression, as detected by immunofluorescence.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	13-26	glial fibrillary acidic protein	Mus musculus	65-96
35163285-8	2022	The systemic tofogliflozin treatment prevented the activation of glial fibrillary acidic protein and VEGF protein expression, as detected by immunofluorescence.	6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol	13-26	vascular endothelial growth factor A	Mus musculus	101-105