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

General Information of Drug (ID: DMD751X)

• Drug Name: 1614235 + 2330672 Drug Info
• Synonyms: AC1LUPX5

Indication

Disease Entry	ICD 11	Status	REF
Type-2 diabetes	5A11	Phase 1	[1]

• Cross-matching ID:
  PubChem CID: 1614235
  TTD Drug ID: DMD751X
  VARIDT Drug ID: DR01118

Molecule-Related Drug Atlas

Drug(s) Targeting Ileal sodium/bile acid cotransporter (SLC10A2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Odevixibat	DMYN391	Pruritus	EC90	Approved	[4]
Maralixibat	DMJCF1O	Pruritus	EC90	Approved	[4]
A-3309	DM4OHMP	Lipid metabolism disorder	5C52.Z	Phase 3	[5]
LUM001	DMQZXDW	Primary biliary cholangitis	DB96.1	Phase 2	[6]
S-8921	DMRZA6G	Hyperlipidaemia	5C80	Phase 2	[7]
264W94	DMBOL4K	Hyperlipidaemia	5C80	Phase 2	[8]
GSK2330672	DM4BTH8	Pruritus	EC90	Phase 2	[9]
Taurocholic Acid	DM2LZ8F	Type-2 diabetes	5A11	Phase 1/2	[10]
AZD-7806	DM34W56	Discovery agent	N.A.	Investigative	[5]

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	[11]
LIK-066	DM32NWD	Heart failure	BD10-BD13	Phase 2	[3]
YG1699	DM1NR1J	Type-1 diabetes	5A10	Phase 2	[12]
GSK1614235	DM7I1AQ	Type-2 diabetes	5A11	Phase 1	[13]
LX2761	DM8ZS7T	Type 2 diabetes	5A11	Phase 1	[14]
T-1095	DMGFS51	Diabetic complication	5A2Y	Discontinued in Phase 2	[15]
KURAIDIN	DMLDUJ1	Discovery agent	N.A.	Investigative	[16]
KURARINONE	DMH0G8W	Discovery agent	N.A.	Investigative	[16]
10-methoxy-N(1)-methylburnamine-17-O-veratrate	DMJW25X	Discovery agent	N.A.	Investigative	[17]
Alstiphyllanine F	DMKRAEW	Discovery agent	N.A.	Investigative	[17]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Ileal sodium/bile acid cotransporter (SLC10A2)	TTPI1M5	NTCP2_HUMAN	Modulator	[2]
Sodium/glucose cotransporter 1 (SGLT1)	TT2UE56	SC5A1_HUMAN	Modulator	[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 800037723)
• [2] 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: 960).
• [3] 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).
• [4] Ileal bile acid transporter inhibition as an anticholestatic therapeutic target in biliary atresia and other cholestatic disorders. Hepatol Int. 2020 Sep;14(5):677-689.
• [5] Elobixibat for the treatment of constipation. Expert Opin Investig Drugs. 2013 Feb;22(2):277-84.
• [6] Current research on the treatment of primary sclerosing cholangitis. Intractable Rare Dis Res. 2015 Feb; 4(1): 1-6.
• [7] Inhibition of ileal Na+/bile acid cotransporter by S-8921 reduces serum cholesterol and prevents atherosclerosis in rabbits. Arterioscler Thromb Vasc Biol. 1998 Aug;18(8):1304-11.
• [8] Inhibition of apical sodium-dependent bile acid transporter as a novel treatment for diabetes. Am J Physiol Endocrinol Metab. 2012 Jan 1;302(1):E68-76.
• [9] Discovery of a highly potent, nonabsorbable apical sodium-dependent bile acid transporter inhibitor (GSK2330672) for treatment of type 2 diabetes. J Med Chem. 2013 Jun 27;56(12):5094-114.
• [10] Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol. 1998 Jan;274(1 Pt 1):G157-69.
• [11] 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.
• [12] 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.
• [13] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [14] Clinical pipeline report, company report or official report of Lexicon Pharmaceuticals.
• [15] T-1095, an inhibitor of renal Na+-glucose cotransporters, may provide a novel approach to treating diabetes. Diabetes. 1999 Sep;48(9):1794-800.
• [16] Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens. Bioorg Med Chem. 2007 May 15;15(10):3445-9.
• [17] 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.