| Identification | Back Directory | [Name]
Cyclohexanecarboxylic acid, 4-[[(3aR,9bR)-9b-[(4-fluorophenyl)sulfonyl]-1,2,3a,4,5,9b-hexahydro-7-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-3H-benz[e]indol-3-yl]carbonyl]-3-methyl-, (1R,3S,4R)- | [CAS]
2460133-35-9 | [Synonyms]
BMS-986251
Cyclohexanecarboxylic acid, 4-[[(3aR,9bR)-9b-[(4-fluorophenyl)sulfonyl]-1,2,3a,4,5,9b-hexahydro-7-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-3H-benz[e]indol-3-yl]carbonyl]-3-methyl-, (1R,3S,4R)- | [Molecular Formula]
C30H29F8NO5S | [MOL File]
2460133-35-9.mol | [Molecular Weight]
667.61 |
| Hazard Information | Back Directory | [Uses]
BMS-986251 is an orally active and selective RORγt inverse agonist with an EC50 of 12 nM for RORγt GAL4. BMS-986251 inhibits IL-17 with an EC50 of 24 nM in human whole blood assay. BMS-986251 demonstrates robust efficacy in mouse acanthosis and Imiquimod-induced (HY-B0180) models (preclinical models of psoriasis)[1]. | [in vivo]
BMS-986251 (5-45 mg/kg; orally; twice daily until day 9) results in reduced ear thickness[1].
BMS-986251 (0.13, 0.79, 4.76 mg/kg; orally; once a day) displays a dose-dependent reduction of the IL-17F produced in na?ve C57BL/6 female mice (7-9 weeks)[1].
BMS-986251 (2 mg/kg of IV and 4 mg/kg of PO) has a T1/2 of 7.7 hours, a CL of 2.7 mL/min?kg, and a Vss of 1.9 L/kg for IV in mouse[1].
| Animal Model: | C57BL/6 female mice with acanthosis[1] | | Dosage: | 5, 15, 45 mg/kg | | Administration: | Orally; twice daily until day 9 | | Result: | Resulted in reduced ear thickness and significantly reduces imiquimod (IMQ)-induced skin thickening.
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| Animal Model: | Mouse or rat[1] | | Dosage: | 2 mg/kg of IV and 4 mg/kg of PO (Pharmacokinetic Analysis) | | Administration: | IV or PO | | Result: | Had a T1/2 of 7.7 hours, a CL of 2.7 mL/min?kg, and a Vss of 1.9 L/kg for IV in mouse.
Had a Cmax of 4.8 μM and an AUC of 37 μM?h for PO in mouse.
Had a T1/2 of 11 hours, a CL of 1.3 mL/min?kg, and a Vss of 1.25 L/kg for IV in rat.
Had a Cmax of 4.7 μM and an AUC of 64 μM?h for PO in rat.
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| [IC 50]
RORγt: 12 nM (EC50); IL-17: 24 nM (EC50); RORα: >10 μM (EC50); RORβ: >10 μM (EC50) | [References]
[1] Robert J. Cherney, et al. Discovery of BMS-986251: A Clinically Viable, Potent, and Selective RORγt Inverse Agonist. ACS Med. Chem. Lett. 2020, 11, 6, 1221–1227 DOI:10.1021/acsmedchemlett.0c00063 |
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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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