| Identification | Back Directory | [Name]
BMS-986339 | [CAS]
2477873-64-4 | [Synonyms]
BMS-986339
Cyclobutanecarboxamide, N-[[4-[5-(1-fluoro-1-methylethyl)-1,2,4-oxadiazol-3-yl]bicyclo[2.2.2]oct-1-yl]methyl]-3-hydroxy-N-[4'-(1-hydroxy-1-methylethyl)[1,1'-biphenyl]-3-yl]-3-(trifluoromethyl)-, cis- | [Molecular Formula]
C35H41F4N3O4 | [MOL File]
2477873-64-4.mol | [Molecular Weight]
643.71 |
| Hazard Information | Back Directory | [Uses]
BMS-986339 is an orally active, potent FXR agonist. BMS-986339 forms H-bond with His298 and ASN287 residues. BMS-986339 can be used in the research of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and nonalcoholic steatohepatitis (NASH), anti-fibrosis[1]. | [in vivo]
BMS-986339 (compound 32, p.o., 10 mg/kg, once daily for 9 days) induces Fgf15 production, and shows antifibrotic efficacy in mouse bile duct ligation (BDL) model[1].
BMS-986339 (p.o. or i.v., 5 mg/kg or 1 mg/kg) exhibits low clearance and a long elimination half-life in mice and rats[1]. | Animal Model: | Mouse bile duct ligation (BDL) model[1] | | Dosage: | 0.3, 1, 3, and 10 mg/kg, once daily for 9 days. | | Administration: | Oral administration | | Result: | Induced Fgf15 and SHP (small heterodimer partner) gene expression to a similar extent in the ileum.
Decreased the ratio of hydroxyproline to the total protein content, and decreased the collagen levels.
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| Animal Model: | Male C57BL6 mice, male Sprague-Dawley rat (pharmacokinetic assay)[1] | | Dosage: | 5 mg/kg or 1 mg/kg | | Administration: | Oral administration, intravenous injection | | Result: | Pharmacokinetic profile of BMS-986339 (compound 32).
| parameter | male C57BL6 mice | male Sprague-Dawley rat | | dose (mg/kg) i.v. | 1 | 1 | | dose (mg/kg) p.o. | 5 | 2 | | Vss (L/kg) i.v. | 2.2 | 5.2 | | AUCtotal (μM?h) i.v. | 16.4 | 6.6 | | AUCtotal (μM?h) p.o. | 56.6 | 5.8 | | t1/2 h (i.v.) | 16 | 18 | | Fp.o. | 69 | 40 |
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| [IC 50]
CYP2C8: 8 μM (IC50); CYP2C9: 13.5 μM (IC50) | [References]
[1] Susheel J Nara, et al. Discovery of BMS-986339, a Pharmacologically Differentiated Farnesoid X Receptor Agonist for the Treatment of Nonalcoholic Steatohepatitis. J Med Chem. 2022 Jul 14;65(13):8948-8960. DOI:10.1021/acs.jmedchem.2c00165 |
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| Company Name: |
Biorbyt Ltd.
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| Tel: |
+44 (0)1223 859 353 |
| Website: |
http://www.biorbyt.com |
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