BMS-986251 是一种具有口服活性的，选择性的RORγt反向激动剂，对 RORγt GAL4 的EC50为12 nM。BMS-986251 抑制IL-17，在人全血分析中EC50为 24 nM。BMS-986251 在小鼠棘皮病和咪喹莫特 (Imiquimod; HY-B0180) 诱导的模型(牛皮癣的临床前模型)中显示出强大的功效。
| 生物活性 | BMS-986251 is an orally active and selectiveRORγtinverse agonist with anEC50of 12 nM for RORγt GAL4. BMS-986251 inhibitsIL-17with anEC50of 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]. |
| IC50& Target[1] | RORγt 12 nM (EC50) | IL-17 24 nM (EC50) | RORα >10 μM (EC50) | RORβ >10 μM (EC50) |
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体外研究
(In Vitro) | BMS-986251 is against ROR family members (RORα GAL4: EC50>10 μM; RORβ GAL4: EC50>10 μM) and against other nuclear receptors (PXR: EC50>5 μM; LXRα: EC50>7.5 μM; LXRβ: EC50>7.5 μM). BMS-986251 does not inhibit any of the CYP’s[1].
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体内研究
(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 naive C57BL/6 female mice (7-9 weeks)[1].
BMS-986251 (2 mg/kg of IV and 4 mg/kg of PO) has a T1/2of 7.7 hours, a CL of 2.7 mL/minokg, and a Vssof 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. |
| 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 T1/2of 7.7 hours, a CL of 2.7 mL/minokg, and a Vssof 1.9 L/kg for IV in mouse.
Had a Cmaxof 4.8 μM and an AUC of 37 μMoh for PO in mouse.
Had a T1/2of 11 hours, a CL of 1.3 mL/minokg, and a Vssof 1.25 L/kg for IV in rat.
Had a Cmaxof 4.7 μM and an AUC of 64 μMoh for PO in rat. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
