Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMGFS51)

• Drug Name: T-1095 Drug Info
• Synonyms: RWJ-394718; T-0687; T-1095A; SGLT-2 inhibitors (diabetes), Tanabe/Johnson & Johnson

Indication

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Discontinued in Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 6918410
  CAS Number: CAS 209746-59-8
  TTD Drug ID: DMGFS51

Molecule-Related Drug Atlas

Drug(s) Targeting Sodium/glucose cotransporter 1 (SGLT1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sotagliflozin	DMMLXA9	Heart failure	BD10-BD13	Approved	[4]
LIK-066	DM32NWD	Heart failure	BD10-BD13	Phase 2	[5]
YG1699	DM1NR1J	Type-1 diabetes	5A10	Phase 2	[6]
1614235 + 2330672	DMD751X	Type-2 diabetes	5A11	Phase 1	[5]
GSK1614235	DM7I1AQ	Type-2 diabetes	5A11	Phase 1	[7]
LX2761	DM8ZS7T	Type 2 diabetes	5A11	Phase 1	[8]
KURAIDIN	DMLDUJ1	Discovery agent	N.A.	Investigative	[9]
KURARINONE	DMH0G8W	Discovery agent	N.A.	Investigative	[9]
10-methoxy-N(1)-methylburnamine-17-O-veratrate	DMJW25X	Discovery agent	N.A.	Investigative	[10]
Alstiphyllanine F	DMKRAEW	Discovery agent	N.A.	Investigative	[10]

Drug(s) Affected By Sodium/glucose cotransporter 2 (SLC5A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[11]
Dapagliflozin	DM28UJG	Non-insulin dependent diabetes	5A11	Approved	[3]
PF-04971729	DM79VXT	Type-2 diabetes	5A11	Approved	[12]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[13]
Canagliflozin	DMFRM1I	Non-insulin dependent diabetes	5A11	Approved	[3]
Bexagliflozin	DMK56G0	Type 2 diabetes	5A11	Approved	[14]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[15]
Urethane	DM7NSI0	N. A.	N. A.	Phase 4	[16]
Remogliflozin etabonate	DMW4YK1	Type-1/2 diabetes	5A10-5A11	Phase 2	[3]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[17]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Sodium/glucose cotransporter 1 (SGLT1)	TT2UE56	SC5A1_HUMAN	Modulator	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Sodium/glucose cotransporter 2 (SLC5A2)	OT93UUDI	SC5A2_HUMAN	Gene/Protein Processing	[3]

References

• [1] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011538)
• [2] T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes. 1999 Sep;48(9):1794-800.
• [3] Discovery of novel N--D-xylosylindole derivatives as sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors for the management of hyperglycemia in diabetes. J Med Chem. 2011 Jan 13;54(1):166-78. doi: 10.1021/jm101072y. Epub 2010 Dec 3.
• [4] 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.
• [5] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 915).
• [6] 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.
• [7] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [8] Clinical pipeline report, company report or official report of Lexicon Pharmaceuticals.
• [9] Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens. Bioorg Med Chem. 2007 May 15;15(10):3445-9.
• [10] Alstiphyllanines E-H, picraline and ajmaline-type alkaloids from Alstonia macrophylla inhibiting sodium glucose cotransporter. Bioorg Med Chem. 2010 Mar 15;18(6):2152-2158.
• [11] Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2020 Jan;28:101321. doi: 10.1016/j.redox.2019.101321. Epub 2019 Sep 5.
• [12] Discovery of a clinical candidate from the structurally unique dioxa-bicyclo[3.2.1]octane class of sodium-dependent glucose cotransporter 2 inhibitors. J Med Chem. 2011 Apr 28;54(8):2952-60. doi: 10.1021/jm200049r. Epub 2011 Mar 30.
• [13] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [14] EGT1442, a potent and selective SGLT2 inhibitor, attenuates blood glucose and HbA(1c) levels in db/db mice and prolongs the survival of stroke-prone rats. Pharmacol Res. 2011 Apr;63(4):284-93. doi: 10.1016/j.phrs.2011.01.001. Epub 2011 Jan 5.
• [15] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [16] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [17] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.