BMS-819881

BMS-819881 is a melaninconcentrating hormone receptor 1 (MCHR1) antagonist, which binds rat MCHR1 with a K_i of 7 nM. BMS-819881 also is selective and potent for CYP3A4 activity with an EC₅₀ of 13 μM. IC50 & Target:Ki: 7 nM (rat MCHR1)^[1]
EC50: 13 μM (CYP3A4)^[1] In Vitro: BMS-819881 (Compound 27) is 99.8% binds to rat serum proteins and rat MCHR1 K_i is 7 nM. FLIPR-based assays establish that BMS-819881 is a potent and highly selective MCHR1 functional antagonist. BMS-819881 (K_b=32 nM) effectively blocks MCH stimulated Ca²⁺ mobilization in heterologous cells overexpressing MCHR1 but fails to inhibit MCH mediated Ca²⁺ mobilization of cells expressing MCHR2 at 10 μM. No activity is observed upon screening BMS-819881 at 10 μM versus a panel of 20 GPCRs associated with feeding homeostasis. The percent of BMS-819881 binds to serum proteins is species dependent ranging from 99.8%, 99.6%, and 99.3%, respectively, for rat, dog, and monkey. When BMS-819881 is screened for cytochrome P450 (CYP) activity, EC₅₀ values for CYP1A2, CYP2C9, CYP2C19, CYP2D6 are >40 μM; however, the CYP3A4 EC₅₀ is 13 μM^[1]. In Vivo: BMS-819881 has moderate terminal elimination half-life (t_1/2=5.7 h, 32±8 h, and 14±3 h for rat (1 mg/kg, iv), dog (1 mg/kg, iv), and cynomologous monkey (1 mg/kg, iv))^[1].