Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTPI1M5)

• DTT Name: Ileal sodium/bile acid cotransporter (SLC10A2)
• Synonyms: Solute carrier family 10 member 2; Sodium/taurocholate cotransporting polypeptide, ileal; SLC10A2; Na(+)dependent ileal bile acid transporter; Ileal sodiumdependent bile acid transporter; Ileal Na(+)/bile acid cotransporter; ISBT; IBAT; Apical sodiumdependent bile acid transporter; ASBT
• Gene Name: SLC10A2
• DTT Type: Clinical trial target; [1]
• UniProt ID: NTCP2_HUMAN
• TTD ID: T24982
• Sequence:
  MNDPNSCVDNATVCSGASCVVPESNFNNILSVVLSTVLTILLALVMFSMGCNVEIKKFLG
  HIKRPWGICVGFLCQFGIMPLTGFILSVAFDILPLQAVVVLIIGCCPGGTASNILAYWVD
  GDMDLSVSMTTCSTLLALGMMPLCLLIYTKMWVDSGSIVIPYDNIGTSLVSLVVPVSIGM
  FVNHKWPQKAKIILKIGSIAGAILIVLIAVVGGILYQSAWIIAPKLWIIGTIFPVAGYSL
  GFLLARIAGLPWYRCRTVAFETGMQNTQLCSTIVQLSFTPEELNVVFTFPLIYSIFQLAF
  AAIFLGFYVAYKKCHGKNKAEIPESKENGTEPESSFYKANGGFQPDEK
• Function: Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine. Plays a key role in cholesterol metabolism.
• KEGG Pathway: Bile secretion (hsa04976)
• Reactome Pathway: Recycling of bile acids and salts (R-HSA-159418)

Molecular Interaction Atlas (MIA) of This DTT

2 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Maralixibat	DMJCF1O	Pruritus	EC90	Approved	[2]
Odevixibat	DMYN391	Pruritus	EC90	Approved	[2]

7 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-3309	DM4OHMP	Lipid metabolism disorder	5C52.Z	Phase 3	[1]
264W94	DMBOL4K	Hyperlipidaemia	5C80	Phase 2	[3]
GSK2330672	DM4BTH8	Pruritus	EC90	Phase 2	[4]
LUM001	DMQZXDW	Primary biliary cholangitis	DB96.1	Phase 2	[5]
S-8921	DMRZA6G	Hyperlipidaemia	5C80	Phase 2	[6]
Taurocholic Acid	DM2LZ8F	Type-2 diabetes	5A11	Phase 1/2	[7]
1614235 + 2330672	DMD751X	Type-2 diabetes	5A11	Phase 1	[8]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AZD-7806	DM34W56	Discovery agent	N.A.	Investigative	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Type 2 diabetes	5A11	Liver tissue	2.54E-01	-0.06	-0.17

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Apical sodium-dependent bile acid transporter (SLC10A2) DTP Info
• Gene Name: SLC10A2

2 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cholic Acid	DM7OKQV	Cholelithiasis	DC11	Approved	[9]
Deoxycholic acid	DM3GYAL	Subcutaneous fat disorder	EF02	Approved	[10]

2 Clinical Trial Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sodium taurocholate	DM3GO0J	Type-2 diabetes	5A11	Phase 1/2	[11]
Taurocholic Acid	DM2LZ8F	Type-2 diabetes	5A11	Phase 1/2	[11]

1 Investigative Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
glycodeoxycholic acid	DM1XEJV	Discovery agent	N.A.	Investigative	[9]

References

• [1] Elobixibat for the treatment of constipation. Expert Opin Investig Drugs. 2013 Feb;22(2):277-84.
• [2] 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.
• [3] 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.
• [4] 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.
• [5] Current research on the treatment of primary sclerosing cholangitis. Intractable Rare Dis Res. 2015 Feb; 4(1): 1-6.
• [6] 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.
• [7] 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.
• [8] 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).
• [9] Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol. 1998 Jan;274(1):G157-69.
• [10] Functional nanoparticles exploit the bile acid pathway to overcome multiple barriers of the intestinal epithelium for oral insulin delivery. Biomaterials. 2018 Jan;151:13-23.
• [11] Identification of a region of the ileal-type sodium/bile acid cotransporter interacting with a competitive bile acid transport inhibitor. Biochemistry. 2002 Dec 17;41(50):14916-24.