Details of the Drug Transporter (DTP)

General Information of Drug Transporter (DTP) (ID: DT7JELC)

• DTP Name: Apical sodium-dependent bile acid transporter (SLC10A2)
• Gene Name: SLC10A2
• UniProt ID: Q12908 (NTCP2_HUMAN)
• VARIDT ID: DTD0020
• Synonyms: ASBT; IBAT; ISBT; Ileal Na(+)/bile acid cotransporter; Ileal sodium-dependent bile acid transporter; Ileal sodium/bile acid cotransporter; NTCP2; Na(+)-dependent ileal bile acid transporter; PBAM; SLC10A2; Sodium/taurocholate cotransporting polypeptide, ileal; Solute carrier family 10 member 2
• DTP Family: Bile Acid:Na(+) Symporter (BASS) Family
• Sequence:
  MNDPNSCVDNATVCSGASCVVPESNFNNILSVVLSTVLTILLALVMFSMGCNVEIKKFLG
  HIKRPWGICVGFLCQFGIMPLTGFILSVAFDILPLQAVVVLIIGCCPGGTASNILAYWVD
  GDMDLSVSMTTCSTLLALGMMPLCLLIYTKMWVDSGSIVIPYDNIGTSLVSLVVPVSIGM
  FVNHKWPQKAKIILKIGSIAGAILIVLIAVVGGILYQSAWIIAPKLWIIGTIFPVAGYSL
  GFLLARIAGLPWYRCRTVAFETGMQNTQLCSTIVQLSFTPEELNVVFTFPLIYSIFQLAF
  AAIFLGFYVAYKKCHGKNKAEIPESKENGTEPESSFYKANGGFQPDEK
• Function: This transporter plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine.
• Endogenous Substrate(s): Bile acids; Bile conjugates; Cholate; Glycochenodeoxycholate
• TCDB ID: 2.A.28.1.2
• Gene ID: 6555
• Reactome Pathway: Recycling of bile acids and salts (R-HSA-159418)

Molecular Interaction Atlas (MIA) of This DTP

2 Approved Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cholic acid	DM7OKQV	Peroxisomal disorder	5C57	Approved	[9]
Deoxycholic acid	DM3GYAL	N. A.	N. A.	Approved	[10]

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	[11]
Taurocholic acid	DM2LZ8F	Type-2 diabetes	5A11	Phase 1/2	[11]

1 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Glycodeoxycholic acid	DM1XEJV	Discovery agent	N.A.	Investigative	[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	6.30E-05	4.95E-02	2.78E-01
Adrenocortical carcinoma	2D11.Z	Kidney	5.28E-01	3.10E-03	1.43E-02
Alopecia	ED70	Skin from scalp	3.01E-01	4.35E-02	1.23E-01
Alzheimer's disease	8A20	Entorhinal cortex	2.76E-01	2.69E-02	1.72E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	3.39E-01	-7.03E-02	-4.91E-01
Aortic stenosis	BB70	Calcified aortic valve	7.92E-01	2.26E-02	3.60E-02
Apnea	7A40	Hyperplastic tonsil	1.31E-01	-1.16E-01	-7.51E-01
Arthropathy	FA00-FA5Z	Peripheral blood	5.10E-01	-1.81E-02	-1.02E-01
Asthma	CA23	Nasal and bronchial airway	4.97E-01	-3.60E-02	-1.61E-01
Atopic dermatitis	EA80	Skin	3.19E-03	-9.80E-02	-7.65E-01
Autism	6A02	Whole blood	2.47E-01	-8.76E-02	-4.74E-01
Autoimmune uveitis	9A96	Peripheral monocyte	6.53E-01	6.57E-02	3.34E-01
Autosomal dominant monocytopenia	4B04	Whole blood	1.18E-01	3.79E-01	1.17E+00
Bacterial infection of gingival	1C1H	Gingival tissue	7.53E-01	3.16E-02	1.48E-01
Batten disease	5C56.1	Whole blood	1.69E-01	-1.58E-02	-1.29E-01
Behcet's disease	4A62	Peripheral blood	2.05E-01	8.24E-02	5.30E-01
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	3.73E-01	9.37E-03	6.09E-02
Bladder cancer	2C94	Bladder tissue	1.28E-03	3.13E-01	1.55E+00
Breast cancer	2C60-2C6Z	Breast tissue	2.79E-05	-4.92E-02	-1.93E-01
Cardioembolic stroke	8B11.20	Whole blood	2.18E-01	7.72E-02	3.68E-01
Cervical cancer	2C77	Cervical tissue	2.83E-01	-3.72E-02	-1.25E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	8.59E-01	-7.34E-03	-3.27E-02
Chronic hepatitis C	1E51.1	Whole blood	7.39E-01	-1.44E-02	-5.43E-02
Chronic obstructive pulmonary disease	CA22	Lung tissue	8.60E-02	7.26E-03	3.84E-02
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	6.10E-01	2.98E-02	1.98E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	2.56E-01	1.64E-01	8.23E-01
Colon cancer	2B90	Colon tissue	2.38E-10	-3.42E-01	-3.78E-01
Coronary artery disease	BA80-BA8Z	Peripheral blood	4.88E-01	-4.15E-02	-1.90E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	8.96E-01	-2.18E-02	-8.24E-02
Endometriosis	GA10	Endometrium tissue	3.91E-01	4.55E-02	2.39E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	4.64E-01	-5.42E-02	-3.98E-01
Familial hypercholesterolemia	5C80.00	Whole blood	4.03E-01	-2.62E-02	-1.26E-01
Gastric cancer	2B72	Gastric tissue	1.42E-13	1.33E-01	5.97E+00
Glioblastopma	2A00.00	Nervous tissue	3.13E-14	-1.10E-01	-3.24E-01
Glioma	2A00.0Y-2A00.0Z	White matter tissue	1.39E-01	-1.03E-01	-4.76E-01
Head and neck cancer	2D42	Head and neck tissue	9.84E-01	9.56E-03	6.10E-02
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	7.22E-02	-7.86E-02	-1.89E-01
Huntington's disease	8A01.10	Whole blood	9.94E-01	2.07E-02	1.21E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	8.11E-01	-1.05E-02	-4.22E-02
Immunodeficiency	4A00-4A20	Peripheral blood	3.17E-01	1.02E-03	1.23E-02
Influenza	1.00E+30	Whole blood	4.17E-03	5.49E-01	3.62E+00
Interstitial cystitis	GC00.3	Bladder tissue	4.97E-01	-6.26E-02	-4.84E-01
Intracranial aneurysm	8B01.0	Intracranial artery	6.37E-01	0.00E+00	0.00E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	5.05E-02	1.29E-01	3.85E-01
Ischemic stroke	8B11	Peripheral blood	1.15E-01	3.80E-02	2.11E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	2.51E-02	1.23E-01	3.82E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	7.21E-01	-9.96E-02	-6.23E-01
Lateral sclerosis	8B60.4	Skin	1.97E-02	2.19E-01	2.21E+00
Liver cancer	2C12.0	Liver tissue	6.93E-02	-8.11E-02	-4.43E-01
Liver failure	DB99.7-DB99.8	Liver tissue	5.66E-01	-1.21E-01	-5.05E-01
Lung cancer	2C25	Lung tissue	1.35E-01	-1.14E-01	-2.16E-01
Lupus erythematosus	4A40	Whole blood	1.05E-01	-8.62E-02	-2.95E-01
Major depressive disorder	6A70-6A7Z	Whole blood	8.92E-01	3.36E-02	1.23E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	4.27E-01	6.85E-03	4.47E-02
Melanoma	2C30	Skin	4.93E-01	-1.09E-01	-2.51E-01
Multiple myeloma	2A83.1	Bone marrow	3.21E-03	-3.36E-01	-1.80E+00
Multiple myeloma	2A83.1	Peripheral blood	6.01E-01	2.88E-02	1.95E-01
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	4.13E-01	-1.24E-01	-6.03E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	2.70E-01	-1.63E-02	-1.17E-01
Myelofibrosis	2A20.2	Whole blood	7.65E-01	-5.18E-02	-3.36E-01
Myocardial infarction	BA41-BA50	Peripheral blood	3.86E-02	1.65E-01	4.16E-01
Myopathy	8C70.6	Muscle tissue	6.12E-01	-4.76E-02	-2.44E-01
Neonatal sepsis	KA60	Whole blood	3.61E-06	1.46E-01	6.73E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	6.51E-04	-7.96E-01	-1.80E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	6.14E-01	1.12E-01	6.69E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	6.20E-01	5.83E-04	5.44E-03
Olive pollen allergy	CA08.00	Peripheral blood	3.61E-01	1.70E-01	1.10E+00
Oral cancer	2B6E	Oral tissue	5.77E-01	-1.35E-01	-4.86E-01
Osteoarthritis	FA00-FA0Z	Synovial tissue	3.24E-01	-1.22E-01	-5.36E-01
Osteoporosis	FB83.1	Bone marrow	6.18E-01	1.46E-02	1.07E-01
Ovarian cancer	2C73	Ovarian tissue	6.48E-01	-6.01E-02	-1.92E-01
Pancreatic cancer	2C10	Pancreas	3.71E-02	-5.36E-01	-1.17E+00
Parkinson's disease	8A00.0	Substantia nigra tissue	4.67E-01	8.62E-02	3.36E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	9.47E-01	-4.49E-02	-2.54E-01
Pituitary cancer	2D12	Pituitary tissue	3.38E-01	-1.03E-02	-7.24E-02
Pituitary gonadotrope tumour	2D12	Pituitary tissue	7.74E-01	7.39E-02	3.77E-01
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	3.81E-02	-4.78E-02	-3.57E-01
Polycythemia vera	2A20.4	Whole blood	5.40E-02	6.06E-02	4.00E-01
Pompe disease	5C51.3	Biceps muscle	1.25E-01	-1.38E-01	-5.86E-01
Preterm birth	KA21.4Z	Myometrium	5.33E-01	-4.22E-02	-3.94E-01
Prostate cancer	2C82	Prostate	2.17E-02	-3.63E-01	-7.03E-01
Psoriasis	EA90	Skin	1.11E-05	-1.60E-01	-5.67E-01
Rectal cancer	2B92	Rectal colon tissue	1.33E-01	-1.62E-01	-7.44E-01
Renal cancer	2C90-2C91	Kidney	3.86E-01	-1.41E+00	-1.10E+00
Retinoblastoma	2D02.2	Uvea	3.20E-03	-1.98E-01	-1.55E+00
Rheumatoid arthritis	FA20	Synovial tissue	3.61E-02	-2.35E-01	-6.56E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	5.12E-01	-4.72E-02	-3.71E-01
Schizophrenia	6A20	Prefrontal cortex	7.82E-01	3.84E-03	1.46E-02
Schizophrenia	6A20	Superior temporal cortex	5.01E-01	-4.38E-03	-2.63E-02
Scleroderma	4A42.Z	Whole blood	4.92E-01	-1.35E-02	-1.17E-01
Seizure	8A60-8A6Z	Whole blood	5.62E-01	4.47E-03	1.86E-02
Sensitive skin	EK0Z	Skin	5.38E-01	0.00E+00	0.00E+00
Sepsis with septic shock	1G41	Whole blood	1.66E-16	2.13E-01	8.61E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	2.60E-01	8.71E-02	5.98E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	1.88E-02	1.63E-01	1.46E+00
Simpson golabi behmel syndrome	LD2C	Adipose tissue	9.15E-01	-4.20E-02	-6.13E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	4.69E-01	-6.69E-02	-1.53E+00
Skin cancer	2C30-2C3Z	Skin	2.08E-11	-2.13E-01	-6.22E-01
Thrombocythemia	3B63	Whole blood	2.66E-01	2.17E-03	1.42E-02
Thrombocytopenia	3B64	Whole blood	5.97E-01	1.14E-02	5.63E-02
Thyroid cancer	2D10	Thyroid	2.51E-01	-1.04E-02	-4.78E-02
Tibial muscular dystrophy	8C75	Muscle tissue	4.07E-01	-1.24E-02	-6.48E-02
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	6.74E-01	4.14E-02	3.32E-01
Type 2 diabetes	5A11	Liver tissue	2.54E-01	-6.48E-02	-1.69E-01
Ureter cancer	2C92	Urothelium	3.62E-02	-7.13E-02	-4.23E-01
Uterine cancer	2C78	Endometrium tissue	9.05E-04	7.97E-02	2.66E-01
Vitiligo	ED63.0	Skin	2.69E-01	-2.66E-01	-7.37E-01

Drug Affinity of This DTP Assessed by Cell Line

Clinical Trial Drug(s)

Drug Name	Highest Status	Cell Line	Affinity	REF
Sodium taurocholate	Phase 1/2	Human embryonic kidney cells (HEK293)-ASBT	Km = 9.4 microM	[11]
Sodium taurocholate	Phase 1/2	Monkey kidney fibroblast-like cell (COS)1-ASBT	Km = 13.3 microM	[12]
Sodium taurocholate	Phase 1/2	Monkey kidney fibroblast-like cell (COS)7-ASBT	Km = 16 microM	[13]
Taurocholic acid	Phase 1/2	Human embryonic kidney cells (HEK293)-ASBT	Km = 9.4 microM	[11]
Taurocholic acid	Phase 1/2	Monkey kidney fibroblast-like cell (COS)1-ASBT	Km = 13.3 microM	[12]

The Drug Therapeutic Target (DTT) Role of This DTP

• DTP DTT Name: Ileal sodium/bile acid cotransporter (SLC10A2) DTT Info
• DTP DTT Type: Clinical trial
• Related Disease:
  Gallbladder/bile ducts/liver structural developmental anomaly [ICD-11: LB20]
  Inborn lipid metabolism error [ICD-11: 5C52]
  Inborn porphyrin/heme metabolism error [ICD-11: 5C58]

9 Clinical Trial Drug(s) Targeting This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
A-3309	DM4OHMP	Lipid metabolism disorder	5C52.Z	Phase 3	[1]
Maralixibat	DMJCF1O	Progressive familial intrahepatic cholestasis	5C58.03	Phase 3	[2]
Odevixibat	DMYN391	Alagille syndrome	LB20.0Y	Phase 3	[2]
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 DTP

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

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.
• [12] 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.
• [13] Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia. Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):2039-45.