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BMS-764459 is a pyrazinone-containing antagonist that targets corticotropin-releasing factor/hormone (CRF or CRH) receptor 1 (CRF1, CRF-R1, CRFR-1, CRH-R1, CRHR-1) with high affinity (IC50 = 0.86 nM against 150 pM ovine CRF for binding rat CRF-R1), potency (IC50 = 1.9 nM against 1 nM CRF-stimulated cAMP production in human Y-79 retinoblastoma cells), and selectivity, displaying little affinity toward CRF-R2/CRF2 and 43 other receptor/channel/transporter proteins (IC50 >10 μM). BMS-764459 exhibits anxiolytic efficacy in a rat defensive withdrawal model of anxiety in vivo (1-3 mg/kg p.o.) with good oral bioavailability (F in dogs = 53% with 2 mg/kg in suspension and 70% with 3 mg/kg in solution).
| Molecular Weight | 405.4 |
| Formula | C19H21F2N5O3 |
| CAS Number | 1188407-45-5 |
| Solubility (25°C) | DMSO: 20 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
[1] Damir Simic, et al. MicroRNA changes associated with atypical CYP1A1 inducer BMS-764459
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