| Identification | Back Directory | [Name]
GSK 2330672 | [CAS]
1345982-69-5 | [Synonyms]
CS-2639
Iinerixibat
linerixibat
GSK 2330672
GSK 2330672; GSK-2330672
Pentanedioic acid, 3-((((3R,5R)-3-butyl-3-ethyl-2,3,4,5-tetrahydro-7-methoxy-1,1-dioxido-5-phenyl-1,4-benzothiazepin-8-yl)methyl)amino)-
3-[[(3R,5R)-3-butyl-3-ethyl-7-methoxy-1,1-dioxo-5-phenyl-4,5-dihydro-2H-1λ6,4-benzothiazepin-8-yl]methylamino]pentanedioic acid | [EINECS(EC#)]
604-604-1 | [Molecular Formula]
C28H38N2O7S | [MDL Number]
MFCD28386358 | [MOL File]
1345982-69-5.mol | [Molecular Weight]
546.68 |
| Chemical Properties | Back Directory | [Boiling point ]
730.8±60.0 °C(Predicted) | [density ]
1.218±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMF: 5 mg/ml; DMSO: 2 mg/ml; PBS (pH 7.2): 0.2 mg/ml | [form ]
A crystalline solid | [pka]
3.27±0.10(Predicted) | [color ]
White to off-white | [InChIKey]
CZGVOBIGEBDYTP-VSGBNLITSA-N | [SMILES]
C(O)(=O)CC(NCC1C=C2S(=O)(=O)C[C@](CCCC)(CC)N[C@H](C3=CC=CC=C3)C2=CC=1OC)CC(O)=O |
| Hazard Information | Back Directory | [Description]
GSK2330672 is an inhibitor of the apical sodium-dependent bile acid transporter (ASBT; IC50s = 42, 2.1, and 1.9 nM for human, mouse, and rat ASBT, respectively).1 In vivo, GSK2330672 (0.05 mg/kg) stimulates fecal bile acid secretion, reduces hemoglobin A1c (HbA1c) and plasma glucose levels, and increases total GLP-1 (Item No. 24460) and plasma insulin in Zucker diabetic fatty (ZDF) rats. | [Uses]
Linerixibat (GSK2330672) is a highly potent, nonabsorbable and orally active apical sodium-dependent bile acid transporter (ASBT) inhibitor with an IC50 of 42 nM human ASBT. Linerixibat can be used as lipid-lowering agent. Linerixibat has the potential for type 2 diabetes and Primary Biliary Cholangitis treatment[1][2][3]. | [in vivo]
Linerixibat (GSK2330672; 0.05-10 mg/kg; oral gavage; twice daily; for 14 days; male ZDF rat) treatment lowers glucose in an animal model of type 2 diabetes[1]. | Animal Model: | Male Zucker Diabetic Fatty (ZDF) rat[1] | | Dosage: | 0.05 mg/kg, 0.1 mg/kg, 0.5 mg/kg, 1 mg/kg, 5 mg/kg, 10 mg/kg | | Administration: | Oral gavage; twice daily; for 14 days | | Result: | Led to a 1.30-1.64% reduction in hemoglobin A1c (HbA1c), a greater than 50% reduction in nonfasted plasma glucose to below 200 mg/dL, and statistically significant higher plasma insulin.
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| [storage]
Store at -20°C | [References]
[1] Wu Y, et al. 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. DOI:10.1021/jm400459m
[2] Wang Y, et al. HNF4α Regulates CSAD to Couple Hepatic Taurine Production to Bile Acid Synthesis in Mice. Gene Expr. 2018 Aug 22;18(3):187-196. DOI:10.3727/105221618X15277685544442
[3] Linerixibat (GSK2330672) granted Orphan Status. September 24, 2019. |
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