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 |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Pruritus [ICD-11: EC90] | |||||
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.
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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 | ||||
HIT2.0 ID | T70FR8 |
Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 2 Approved Drugs | + | ||||
1 | Maralixibat | Drug Info | Approved | Pruritus | [2] | |
2 | Odevixibat | Drug Info | Approved | Pruritus | [3] | |
Clinical Trial Drug(s) | [+] 7 Clinical Trial Drugs | + | ||||
1 | A-3309 | Drug Info | Phase 3 | Lipid metabolism disorder | [4] | |
2 | 264W94 | Drug Info | Phase 2 | Hyperlipidaemia | [5], [6] | |
3 | GSK2330672 | Drug Info | Phase 2 | Type-2 diabetes | [7] | |
4 | LUM001 | Drug Info | Phase 2 | Primary biliary cirrhosis | [8] | |
5 | S-8921 | Drug Info | Phase 2 | Hyperlipidaemia | [9] | |
6 | Taurocholic Acid | Drug Info | Phase 1/2 | Type-2 diabetes | [10] | |
7 | 1614235 + 2330672 | Drug Info | Phase 1 | Type-2 diabetes | [11] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 5 Inhibitor drugs | + | ||||
1 | Maralixibat | Drug Info | [12] | |||
2 | Odevixibat | Drug Info | [12] | |||
3 | A-3309 | Drug Info | [1] | |||
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] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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Bile secretion | hsa04976 | Affiliated Target |
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Class: Organismal Systems => Digestive system | Pathway Hierarchy |
Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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Closeness centrality | 1.39E-01 | Radiality | 1.15E+01 | Clustering coefficient | 0.00E+00 |
Neighborhood connectivity | 2.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 13 |
Download | Click to Download the Full PPI Network of This Target | ||||
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 | FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 214662. | |||||
REF 3 | FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 215498. | |||||
REF 4 | ClinicalTrials.gov (NCT01895543) Safety and Tolerability Extension Trial for Patients With Chronic Idiopathic Constipation. 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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