Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT56EKP)

• DTP Name: Sodium/taurocholate cotransporting polypeptide (SLC10A1)
• Gene Name: SLC10A1
• UniProt ID: Q14973 (NTCP_HUMAN)
• VARIDT ID: DTD0019
• Synonyms: Cell growth-inhibiting gene 29 protein; NTCP; Na(+)/bile acid cotransporter; Na(+)/taurocholate transport protein; SLC10A1; Sodium/bile acid cotransporter; Solute carrier family 10 member 1
• DTP Family: Bile Acid:Na(+) Symporter (BASS) Family
• Sequence:
  MEAHNASAPFNFTLPPNFGKRPTDLALSVILVFMLFFIMLSLGCTMEFSKIKAHLWKPKG
  LAIALVAQYGIMPLTAFVLGKVFRLKNIEALAILVCGCSPGGNLSNVFSLAMKGDMNLSI
  VMTTCSTFCALGMMPLLLYIYSRGIYDGDLKDKVPYKGIVISLVLVLIPCTIGIVLKSKR
  PQYMRYVIKGGMIIILLCSVAVTVLSAINVGKSIMFAMTPLLIATSSLMPFIGFLLGYVL
  SALFCLNGRCRRTVSMETGCQNVQLCSTILNVAFPPEVIGPLFFFPLLYMIFQLGEGLLL
  IAIFWCYEKFKTPKDKTKMIYTAATTEETIPGALGNGTYKGEDCSPCTA
• Function: This tranporter strictly dependent on the extracellular presence of sodium and exhibits broad substrate specificity and transports various non-bile acid organic compounds as well.
• Endogenous Substrate(s): Bile acids; Bile conjugates; Steroids; Cholate; Tauroursodeoxycholate
• TCDB ID: 2.A.28.1.9
• Gene ID: 6554
• 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 DTP

5 Approved Drug(s) Transported by This DTP

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 DTP

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]

Molecular Expression Atlas (MEA) of This DTP

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	4.24E-01	-2.01E-02	-1.07E-01
Adrenocortical carcinoma	2D11.Z	Kidney	5.61E-01	-5.66E-02	-2.24E-01
Alopecia	ED70	Skin from scalp	2.33E-02	-8.08E-02	-3.94E-01
Alzheimer's disease	8A20	Entorhinal cortex	4.99E-01	-3.21E-02	-1.52E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	2.41E-01	-1.46E-01	-9.51E-01
Aortic stenosis	BB70	Calcified aortic valve	6.72E-01	1.91E-03	1.75E-03
Apnea	7A40	Hyperplastic tonsil	4.96E-01	1.17E-01	2.20E-01
Arthropathy	FA00-FA5Z	Peripheral blood	3.16E-01	8.97E-02	4.87E-01
Asthma	CA23	Nasal and bronchial airway	1.37E-02	-2.49E-02	-3.57E-02
Atopic dermatitis	EA80	Skin	3.05E-01	-1.27E-02	-9.08E-02
Autism	6A02	Whole blood	2.67E-01	-8.35E-03	-3.09E-02
Autoimmune uveitis	9A96	Peripheral monocyte	9.15E-03	-2.41E-01	-7.55E-01
Autosomal dominant monocytopenia	4B04	Whole blood	9.94E-01	-3.60E-02	-3.13E-01
Bacterial infection of gingival	1C1H	Gingival tissue	8.20E-01	-3.96E-02	-7.20E-02
Batten disease	5C56.1	Whole blood	1.92E-01	1.36E-01	9.84E-01
Behcet's disease	4A62	Peripheral blood	8.08E-01	9.03E-02	3.79E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	1.48E-01	-8.12E-02	-3.77E-01
Bladder cancer	2C94	Bladder tissue	5.18E-05	1.01E+00	3.48E+00
Breast cancer	2C60-2C6Z	Breast tissue	1.92E-11	-1.63E-01	-4.52E-01
Cardioembolic stroke	8B11.20	Whole blood	3.38E-01	-2.30E-01	-5.64E-01
Cervical cancer	2C77	Cervical tissue	3.06E-01	-2.36E-01	-6.50E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	5.20E-01	2.46E-03	1.48E-02
Chronic hepatitis C	1E51.1	Whole blood	7.56E-02	6.06E-02	5.73E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	2.39E-02	1.76E-01	6.90E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	3.33E-01	-3.78E-02	-1.60E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	1.56E-01	1.06E-01	4.59E-01
Colon cancer	2B90	Colon tissue	4.71E-02	-1.32E-01	-4.26E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	6.94E-01	-6.97E-02	-5.73E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	5.64E-01	-9.35E-02	-5.90E-01
Endometriosis	GA10	Endometrium tissue	7.43E-01	-1.65E-02	-4.47E-02
Familial hypercholesterolemia	5C80.00	Peripheral blood	7.72E-01	5.07E-03	2.85E-02
Familial hypercholesterolemia	5C80.00	Whole blood	7.48E-02	-5.70E-02	-2.14E-01
Gastric cancer	2B72	Gastric tissue	4.66E-01	-3.22E-01	-1.03E+00
Glioblastopma	2A00.00	Nervous tissue	3.23E-11	-1.41E-01	-3.51E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	1.39E-05	-8.80E-01	-3.37E+00
Head and neck cancer	2D42	Head and neck tissue	1.19E-06	-8.84E-02	-4.25E-01
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	7.56E-02	-4.68E-02	-1.49E-01
Huntington's disease	8A01.10	Whole blood	7.20E-01	-7.45E-02	-4.72E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	6.08E-01	-1.62E-02	-6.26E-02
Immunodeficiency	4A00-4A20	Peripheral blood	6.44E-01	2.10E-02	1.96E-01
Influenza	1.00E+30	Whole blood	2.21E-02	5.45E-01	2.66E+00
Interstitial cystitis	GC00.3	Bladder tissue	5.40E-01	-2.87E-02	-2.67E-01
Intracranial aneurysm	8B01.0	Intracranial artery	3.43E-01	7.09E-02	3.92E-01
Irritable bowel syndrome	DD91.0	Rectal colon tissue	6.12E-01	-2.38E-02	-6.83E-02
Ischemic stroke	8B11	Peripheral blood	6.06E-03	6.75E-02	3.80E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	7.75E-02	3.07E-02	1.07E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	5.74E-01	1.62E-01	4.70E-01
Lateral sclerosis	8B60.4	Skin	2.64E-01	2.52E-02	1.90E-01
Liver cancer	2C12.0	Liver tissue	2.22E-20	-2.47E+00	-2.18E+00
Liver failure	DB99.7-DB99.8	Liver tissue	1.12E-05	-3.42E+00	-4.07E+00
Lung cancer	2C25	Lung tissue	2.00E-01	-3.18E-02	-1.27E-01
Lupus erythematosus	4A40	Whole blood	1.41E-01	-7.09E-03	-1.31E-02
Major depressive disorder	6A70-6A7Z	Whole blood	9.13E-03	-7.01E-02	-2.07E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	9.07E-01	-9.65E-03	-4.84E-02
Melanoma	2C30	Skin	6.96E-01	1.78E-01	1.41E-01
Multiple myeloma	2A83.1	Bone marrow	1.21E-03	-4.83E-01	-2.00E+00
Multiple myeloma	2A83.1	Peripheral blood	2.13E-01	1.57E-01	7.50E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	2.01E-01	7.36E-02	1.35E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	1.86E-01	-4.48E-02	-1.55E-01
Myelofibrosis	2A20.2	Whole blood	1.57E-01	4.27E-02	3.16E-01
Myocardial infarction	BA41-BA50	Peripheral blood	2.41E-01	-6.38E-02	-6.88E-02
Myopathy	8C70.6	Muscle tissue	2.45E-01	-1.50E-01	-6.52E-01
Neonatal sepsis	KA60	Whole blood	5.15E-01	-4.80E-02	-2.12E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	1.48E-04	-1.05E+00	-1.98E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	4.33E-01	-2.18E-01	-5.91E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	3.21E-01	1.23E-01	1.16E+00
Olive pollen allergy	CA08.00	Peripheral blood	1.65E-01	1.29E-01	8.50E-01
Oral cancer	2B6E	Oral tissue	2.83E-03	-4.60E-01	-1.02E+00
Osteoarthritis	FA00-FA0Z	Synovial tissue	9.35E-01	-9.79E-02	-3.34E-01
Osteoporosis	FB83.1	Bone marrow	1.31E-01	1.26E-01	9.96E-01
Ovarian cancer	2C73	Ovarian tissue	5.12E-01	-1.69E-01	-7.38E-01
Pancreatic cancer	2C10	Pancreas	5.00E-01	-3.38E-01	-9.45E-01
Parkinson's disease	8A00.0	Substantia nigra tissue	8.18E-01	1.70E-02	6.00E-02
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	5.80E-01	-3.65E-02	-2.72E-01
Pituitary cancer	2D12	Pituitary tissue	6.22E-01	1.56E-01	4.20E-01
Pituitary gonadotrope tumour	2D12	Pituitary tissue	8.68E-01	-3.93E-02	-1.42E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	3.43E-01	-5.05E-02	-2.32E-01
Polycythemia vera	2A20.4	Whole blood	4.06E-01	1.76E-02	1.20E-01
Pompe disease	5C51.3	Biceps muscle	5.31E-01	9.50E-02	5.46E-01
Preterm birth	KA21.4Z	Myometrium	1.35E-01	-2.03E-01	-1.20E+00
Prostate cancer	2C82	Prostate	4.62E-04	-1.56E+00	-1.46E+00
Psoriasis	EA90	Skin	8.64E-13	-3.69E-01	-8.82E-01
Rectal cancer	2B92	Rectal colon tissue	9.81E-01	-6.29E-02	-3.15E-01
Renal cancer	2C90-2C91	Kidney	3.64E-04	-6.11E-01	-1.64E+00
Retinoblastoma	2D02.2	Uvea	1.74E-04	-4.29E-01	-5.34E+00
Rheumatoid arthritis	FA20	Synovial tissue	2.46E-01	-1.12E-01	-3.98E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	7.19E-01	1.77E-03	1.05E-02
Schizophrenia	6A20	Prefrontal cortex	4.90E-01	4.02E-03	9.07E-03
Schizophrenia	6A20	Superior temporal cortex	6.51E-01	-3.74E-02	-1.87E-01
Scleroderma	4A42.Z	Whole blood	1.29E-04	-3.20E-01	-2.06E+00
Seizure	8A60-8A6Z	Whole blood	9.66E-01	2.74E-03	1.10E-02
Sensitive skin	EK0Z	Skin	5.86E-01	-2.19E-03	-2.01E-02
Sepsis with septic shock	1G41	Whole blood	3.52E-02	5.37E-02	2.03E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	1.38E-01	5.93E-01	1.10E+00
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	1.77E-01	2.51E-01	7.17E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	1.31E-01	-2.66E-02	-4.96E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	6.09E-01	1.74E-02	4.88E-02
Skin cancer	2C30-2C3Z	Skin	1.29E-01	-7.84E-02	-1.20E-01
Thrombocythemia	3B63	Whole blood	1.80E-01	-2.16E-03	-1.42E-02
Thrombocytopenia	3B64	Whole blood	2.90E-01	9.09E-02	5.67E-01
Thyroid cancer	2D10	Thyroid	7.46E-03	5.72E-02	2.22E-01
Tibial muscular dystrophy	8C75	Muscle tissue	2.87E-01	7.95E-02	3.22E-01
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	5.38E-02	1.63E-01	4.22E+00
Type 2 diabetes	5A11	Liver tissue	2.93E-01	2.87E-02	1.38E-01
Ureter cancer	2C92	Urothelium	1.13E-01	-1.40E-01	-4.52E-01
Uterine cancer	2C78	Endometrium tissue	2.01E-01	2.51E-02	6.33E-02
Vitiligo	ED63.0	Skin	8.44E-01	1.16E-02	5.99E-02

Drug Affinity of This DTP Assessed by Cell Line

Approved Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
PITAVASTATIN CALCIUM	Approved	Oocytes-NTCP	Km = 15.1 microM	[6]
Rosuvastatin	Approved	Human cervical cancer cell line (Hela)-NTCP	Km = 65.0 microM	[7]

Clinical Trial Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Sodium taurocholate	Phase 1/2	Human cervical cancer cell line (Hela)-NTCP	Km = 7.5 microM	[4]
Sodium taurocholate	Phase 1/2	Human cervical cancer cell line (Hela)-NTCP	Km = 7.9 microM	[9]
Sodium taurocholate	Phase 1/2	Human embryonic kidney cells (HEK293)-NTCP	Km = 2.1 microM	[8]
Taurocholic Acid	Phase 1/2	Human cervical cancer cell line (Hela)-NTCP	Km = 7.9 microM	[9]
Taurocholic Acid	Phase 1/2	Oocytes-NTCP	Km = 6.2 microM	[10]

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Sodium/bile acid cotransporter (SLC10A1) DTT Info
• DTP DTT Type: Successful

1 Approved Drug(s) Targeting This DTP

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

1 Clinical Trial Drug(s) Targeting This DTP

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

References

• [1] Bulevirtide: First Approval. Drugs. 2020 Oct;80(15):1601-1605.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [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.
• [10] Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. J Clin Invest. 1994 Mar;93(3):1326-31.