CP671305

445295-04-5

C23H19FN2O7

DMSO : >= 160 mg/mL (352.11 mM)

Metabolic Enzyme/Protease

CP671305 is a potent, orally active, selective inhibitor of phosphodiesterase-4-D, and possesses high activities. In Vitro: CP-671, 305 is identified as a substrate of MRP2 and BCRP, but not MDR1. CP-671, 305 is a substrate of human OATP2B1 with a high affinity (K_m=4 uM) but not a substrate for human OATP1B1 or OATP1B3. CP-671, 305 displays high affinity (K_m=12 uM) for rat hepatic Oatp1a4^[1]. CP-671, 305 does not exhibit competitive inhibition of the five major cytochrome P450 enzymes, namely CYP1A2, 2C9, 2C19, 2D6 and 3A4 (IC₅₀s >?50 uM). Likewise, no time-dependent inactivation of the five major cytochrome P450 enzymes is discernible with CP-671, 305^[2]. In Vivo: CP-671, 305 pharmacokinetics are largely unaltered, and compromised biliary clearance of CP-671, 305 is compensated by increased urinary clearance^[1]. CP-671, 305 demonstrates generally favourable pharmacokinetic properties, systemic plasma clearance after intravenous administration is low in Sprague-Dawley rats (9.60?+/-?1.16?mL/min/kg), beagle dogs (2.90?+/-?0.81?mL/min/kg) and cynomolgus monkeys (2.94?+/-?0.87?mL/min/kg) resulting in plasma half-lives >?5?h. Moderate to high bioavailability in rats (43-80%), dogs (45%) and monkeys (26%) is observed after oral dosing. In rats, oral pharmacokinetics are dose dependent over the dose range studied (10 and 25?mg/kg)^[2].