Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTWZRY5)

• DTT Name: Sodium/bile acid cotransporter (SLC10A1)
• Synonyms: Solute carrier family 10 member 1; Sodium/taurocholate cotransporting polypeptide; Na(+)/taurocholate transport protein; Na(+)/bile acid cotransporter; Cell growth-inhibiting gene 29 protein
• Gene Name: SLC10A1
• DTT Type: Successful target; [1]
• BioChemical Class: Bile acid:sodium symporter (BASS) (TC 2.A.28) family
• UniProt ID: NTCP_HUMAN
• TTD ID: T99189
• Sequence:
  MEAHNASAPFNFTLPPNFGKRPTDLALSVILVFMLFFIMLSLGCTMEFSKIKAHLWKPKG
  LAIALVAQYGIMPLTAFVLGKVFRLKNIEALAILVCGCSPGGNLSNVFSLAMKGDMNLSI
  VMTTCSTFCALGMMPLLLYIYSRGIYDGDLKDKVPYKGIVISLVLVLIPCTIGIVLKSKR
  PQYMRYVIKGGMIIILLCSVAVTVLSAINVGKSIMFAMTPLLIATSSLMPFIGFLLGYVL
  SALFCLNGRCRRTVSMETGCQNVQLCSTILNVAFPPEVIGPLFFFPLLYMIFQLGEGLLL
  IAIFWCYEKFKTPKDKTKMIYTAATTEETIPGALGNGTYKGEDCSPCTA
• Function: The hepatic sodium/bile acid uptake system exhibits broad substrate specificity and transports various non-bile acid organic compounds as well. It is strictly dependent on the extracellular presence of sodium.
• KEGG Pathway:
  Bile secretion (hsa04976)
  Hepatitis B (hsa05161)
• Reactome Pathway: Recycling of bile acids and salts (R-HSA-159418)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Bulevirtide	DMJUVE6	Hepatitis D virus infection	1E51.2	Approved	[2]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LUM001	DMQZXDW	Primary biliary cholangitis	DB96.1	Phase 2	[1]

The Drug Transporter (DTP) Role of This DTT

• DTT DTP Name: Sodium/taurocholate cotransporting polypeptide (SLC10A1) DTP Info
• Gene Name: SLC10A1

5 Approved Drug(s) Transported by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cerivastatin	DMXCM7H	Hyperlipidaemia	5C80	Approved	[3]
Estrone sulfate	DMVBIZL	Atrophic vaginitis	GA30.2	Approved	[4]
Liothyronine	DM6IR3P	Congenital hypothyroidism		Approved	[5]
PITAVASTATIN CALCIUM	DM1UJO0	Dyslipidemia	5C80-5C81	Approved	[6]
Rosuvastatin	DMMIQ7G	Arteriosclerosis	BD40	Approved	[7]

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	[8]
Taurocholic Acid	DM2LZ8F	Type-2 diabetes	5A11	Phase 1/2	[9]

References

• [1] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [2] Bulevirtide: First Approval. Drugs. 2020 Oct;80(15):1601-1605.
• [3] Differential effect of genetic variants of Na(+)-taurocholate co-transporting polypeptide (NTCP) and organic anion-transporting polypeptide 1B1 (OATP1B1) on the uptake of HMG-CoA reductase inhibitors. Xenobiotica. 2011 Jan;41(1):24-34.
• [4] Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition. J Biol Chem. 2004 Feb 20;279(8):7213-22.
• [5] Identification of thyroid hormone transporters. Biochem Biophys Res Commun. 1999 Jan 19;254(2):497-501.
• [6] Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
• [7] Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics. Gastroenterology. 2006 May;130(6):1793-806.
• [8] Differential inhibition of rat and human Na+-dependent taurocholate cotransporting polypeptide (NTCP/SLC10A1)by bosentan: a mechanism for species differences in hepatotoxicity. J Pharmacol Exp Ther. 2007 Jun;321(3):1170-8.
• [9] Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J Pharmacol Exp Ther. 1999 Dec;291(3):1204-9.