Target Information
| Target General Information | Top | |||||
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| Target ID |
T24982
(Former ID: TTDNC00442)
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| Target Name |
Ileal sodium/bile acid cotransporter (SLC10A2)
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| 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
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| Gene Name |
SLC10A2
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Gallbladder/bile ducts/liver structural developmental anomaly [ICD-11: LB20] | |||||
| 2 | Inborn lipid metabolism error [ICD-11: 5C52] | |||||
| 3 | Inborn porphyrin/heme metabolism error [ICD-11: 5C58] | |||||
| 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.
Click to Show/Hide
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| UniProt ID | ||||||
| Sequence |
MNDPNSCVDNATVCSGASCVVPESNFNNILSVVLSTVLTILLALVMFSMGCNVEIKKFLG
HIKRPWGICVGFLCQFGIMPLTGFILSVAFDILPLQAVVVLIIGCCPGGTASNILAYWVD GDMDLSVSMTTCSTLLALGMMPLCLLIYTKMWVDSGSIVIPYDNIGTSLVSLVVPVSIGM FVNHKWPQKAKIILKIGSIAGAILIVLIAVVGGILYQSAWIIAPKLWIIGTIFPVAGYSL GFLLARIAGLPWYRCRTVAFETGMQNTQLCSTIVQLSFTPEELNVVFTFPLIYSIFQLAF AAIFLGFYVAYKKCHGKNKAEIPESKENGTEPESSFYKANGGFQPDEK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 9 Clinical Trial Drugs | + | ||||
| 1 | A-3309 | Drug Info | Phase 3 | Lipid metabolism disorder | [2] | |
| 2 | Maralixibat | Drug Info | Phase 3 | Progressive familial intrahepatic cholestasis | [3] | |
| 3 | Odevixibat | Drug Info | Phase 3 | Alagille syndrome | [4] | |
| 4 | 264W94 | Drug Info | Phase 2 | Hyperlipidaemia | [5], [6] | |
| 5 | GSK2330672 | Drug Info | Phase 2 | Type-2 diabetes | [7] | |
| 6 | LUM001 | Drug Info | Phase 2 | Primary biliary cirrhosis | [8] | |
| 7 | S-8921 | Drug Info | Phase 2 | Hyperlipidaemia | [9] | |
| 8 | Taurocholic Acid | Drug Info | Phase 1/2 | Type-2 diabetes | [10] | |
| 9 | 1614235 + 2330672 | Drug Info | Phase 1 | Type-2 diabetes | [11] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 5 Inhibitor drugs | + | ||||
| 1 | A-3309 | Drug Info | [1] | |||
| 2 | Maralixibat | Drug Info | [12] | |||
| 3 | Odevixibat | Drug Info | [12] | |||
| 4 | LUM001 | Drug Info | [13] | |||
| 5 | S-8921 | Drug Info | [9] | |||
| Modulator | [+] 5 Modulator drugs | + | ||||
| 1 | 264W94 | Drug Info | [6] | |||
| 2 | GSK2330672 | Drug Info | [7] | |||
| 3 | Taurocholic Acid | Drug Info | [14] | |||
| 4 | 1614235 + 2330672 | Drug Info | [15] | |||
| 5 | AZD-7806 | Drug Info | [1] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 1 KEGG Pathways | + | ||||
| 1 | Bile secretion | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Recycling of bile acids and salts | |||||
| WikiPathways | [+] 1 WikiPathways | + | ||||
| 1 | Bile acid and bile salt metabolism | |||||
| References | Top | |||||
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| REF 1 | Elobixibat for the treatment of constipation. Expert Opin Investig Drugs. 2013 Feb;22(2):277-84. | |||||
| REF 2 | ClinicalTrials.gov (NCT01895543) Safety and Tolerability Extension Trial for Patients With Chronic Idiopathic Constipation. U.S. National Institutes of Health. | |||||
| REF 3 | ClinicalTrials.gov (NCT04185363) An Extension Study of Maralixibat in Patients With Progressive Familial Intrahepatic Cholestasis (PFIC). U.S. National Institutes of Health. | |||||
| REF 4 | ClinicalTrials.gov (NCT04674761) Efficacy and Safety of Odevixibat in Patients With Alagille Syndrome (ASSERT). U.S. National Institutes of Health. | |||||
| REF 5 | 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. (Ligand id: 6529). | |||||
| REF 6 | 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. | |||||
| REF 7 | 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. | |||||
| REF 8 | ClinicalTrials.gov (NCT02321306) An Open-label Study to Evaluate the Long-term Safety and Tolerability of LUM001 in Patients With Primary Biliary Cirrhosis. U.S. National Institutes of Health. | |||||
| REF 9 | 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. | |||||
| REF 10 | 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. (Ligand id: 4547). | |||||
| REF 11 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037723) | |||||
| REF 12 | 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. | |||||
| REF 13 | Current research on the treatment of primary sclerosing cholangitis. Intractable Rare Dis Res. 2015 Feb; 4(1): 1-6. | |||||
| REF 14 | 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. | |||||
| REF 15 | 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). | |||||
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