Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTLWPVF)

• DTT Name: Sodium/glucose cotransporter 2 (SGLT2)
• Synonyms: Solute carrier family 5 member 2; Na(+)/glucose cotransporter 2; Low affinity sodium-glucose cotransporter
• Gene Name: SLC5A2
• DTT Type: Successful target; [1]
• BioChemical Class: Solute:sodium symporter
• UniProt ID: SC5A2_HUMAN
• TTD ID: T30085
• Sequence:
  MEEHTEAGSAPEMGAQKALIDNPADILVIAAYFLLVIGVGLWSMCRTNRGTVGGYFLAGR
  SMVWWPVGASLFASNIGSGHFVGLAGTGAASGLAVAGFEWNALFVVLLLGWLFAPVYLTA
  GVITMPQYLRKRFGGRRIRLYLSVLSLFLYIFTKISVDMFSGAVFIQQALGWNIYASVIA
  LLGITMIYTVTGGLAALMYTDTVQTFVILGGACILMGYAFHEVGGYSGLFDKYLGAATSL
  TVSEDPAVGNISSFCYRPRPDSYHLLRHPVTGDLPWPALLLGLTIVSGWYWCSDQVIVQR
  CLAGKSLTHIKAGCILCGYLKLTPMFLMVMPGMISRILYPDEVACVVPEVCRRVCGTEVG
  CSNIAYPRLVVKLMPNGLRGLMLAVMLAALMSSLASIFNSSSTLFTMDIYTRLRPRAGDR
  ELLLVGRLWVVFIVVVSVAWLPVVQAAQGGQLFDYIQAVSSYLAPPVSAVFVLALFVPRV
  NEQGAFWGLIGGLLMGLARLIPEFSFGSGSCVQPSACPAFLCGVHYLYFAIVLFFCSGLL
  TLTVSLCTAPIPRKHLHRLVFSLRHSKEEREDLDADEQQGSSLPVQNGCPESAMEMNEPQ
  APAPSLFRQCLLWFCGMSRGGVGSPPPLTQEEAAAAARRLEDISEDPSWARVVNLNALLM
  MAVAVFLWGFYA
• Function: Has a Na(+) to glucose coupling ratio of 1:1. Sodium-dependent glucose transporter.
• Reactome Pathway:
  Na+-dependent glucose transporters (R-HSA-428808)
  Inositol transporters (R-HSA-429593)
  Hexose transport (R-HSA-189200)

Molecular Interaction Atlas (MIA) of This DTT

6 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Canagliflozin	DMFRM1I	Non-insulin dependent diabetes	5A11	Approved	[2]
Dapagliflozin	DM28UJG	Non-insulin dependent diabetes	5A11	Approved	[1]
Dapagliflozin Propanediol; Saxagliptin Hydrochloride	DM34TXO	Type-2 diabetes	5A11	Approved	[3]
Empagliflozin	DMRF9YK	Type-1 diabetes	5A10	Approved	[1]
PF-04971729	DM79VXT	Type-2 diabetes	5A11	Approved	[4]
Sotagliflozin	DMMLXA9	Heart failure	BD10-BD13	Approved	[5]

9 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ASP1941	DMGQ1TV	Liver disease	DB90-BD99	Phase 3	[6]
AVE-2268	DMA42BV	Diabetic complication	5A2Y	Phase 2	[7]
LIK-066	DM32NWD	Heart failure	BD10-BD13	Phase 2	[8]
Remogliflozin etabonate	DMW4YK1	Type-1/2 diabetes	5A10-5A11	Phase 2	[9]
RO-4998452	DMZJREM	Type-2 diabetes	5A11	Phase 2	[10]
YG1699	DM1NR1J	Type-1 diabetes	5A10	Phase 2	[11]
YM-543	DMRZBPI	Type-2 diabetes	5A11	Phase 2	[12]
BI-44847	DM2KVM0	Type-2 diabetes	5A11	Phase 1	[13]
EGT-0001474	DMDPGCS	Type-2 diabetes	5A11	Phase 1	[14]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TS-033	DMALIFO	Diabetic complication	5A2Y	Discontinued in Phase 2	[15]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Empagli ozin	DMQLNZC	Type-2 diabetes	5A11	Investigative	[1]
sergliflozin	DMF8GAX	Discovery agent	N.A.	Investigative	[16]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Sodium/glucose cotransporter 2 (SLC5A2) DTP Info
• Gene Name: SLC5A2

1 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
D-glucose	DMMG2TO	Discovery agent	N.A.	Investigative	[17]

References

• [1] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [2] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Dose-ranging efficacy and safety study of ertugliflozin, a sodium-glucose co-transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin.Diabetes Obes Metab.2015 Jun;17(6):591-8.
• [5] LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther. 2012 Aug;92(2):158-69.
• [6] Ipragliflozin: A novel sodium-glucose cotransporter 2 inhibitor developed in Japan.World J Diabetes.2015 Feb 15;6(1):136-44.
• [7] Effects of AVE2268, a substituted glycopyranoside, on urinary glucose excretion and blood glucose in mice and rats. Arzneimittelforschung. 2008;58(11):574-80.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus.Diabetes Obes Metab.2015 Oct;17(10):984-93.
• [11] ClinicalTrials.gov (NCT04956263) A Comparison of Postprandial Glucose After a Mixed Meal Tolerance Test, and the Metabolic Effects of Insulin Withdrawal in a Crossover Study of the Dual Systemic SGLT1 and SGLT2 Inhibitor YG1699, and the Selective SGLT2 Inhibitor Dapagliflozin in Subjects With Type 1 Diabetes. U.S.National Institutes of Health.
• [12] Pharmacological Characterization of YM543, a Newly Synthesized, Orally Active SGLT2 Selective Inhibitor. Endocr Res. 2013 Aug;38(3):168-183.
• [13] Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes
• [14] PhRMA report
• [15] Company report (Taisho)
• [16] Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal gluco... J Pharmacol Exp Ther. 2007 Jan;320(1):323-30.
• [17] The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing. PLoS One. 2014 Feb 26;9(2):e89977.