CP-100356 (hydrochloride)

CP-100356 hydrochloride is an orally active dual MDR1 (P-gp)/BCRP inhibitor, with an IC₅₀s of 0.5 and 1.5 µM for inhibiting MDR1-mediated Calcein-AM transport and BCRP-mediated Prazosin transport, respectively. CP-100356 hydrochloride is also a weak inhibitor of OATP1B1 (IC₅₀=∼66 µM). CP-100356 hydrochloride is devoid of inhibition against MRP2 and major human P450 enzymes (IC₅₀>15 µM)^[1]. IC50 & Target: IC50: 0.5 µM (MDR1), 1.5 µM (BCRP) in MDCKII cells^[1] In Vitro: CP-100356 (0.1-15 µM; pretreated for 30 min) inhibits acetoxymethyl Calcein (Calcein-AM) uptake and and Digoxin transport in human MDR1-transfected MDCKII cells, with IC₅₀s of 0.50 µM and 1.2 µM, respectively. CP-100356 decreases the BCRP-mediated transport of Prazosin in MDCKII cells, with an IC₅₀ of 1.5 µM^[1].
CP-100356 (0.064-200 µM; 5 min) inhibits OATP1B1-mediated uptake of Estradiol 17β-D-Glucuronide, with an IC₅₀ of ~66 µM^[1].
CP-100356 (0-50 µM; 10-30 min) is devoid of inhibition (IC₅₀>50 µM) against the catalytic activity of the individual P450 enzymes including P4503A4 in the competitive inhibition study^[1]. In Vivo: CP-100356 (6-24 mg/kg; p.o.) increases the systemic exposure of Fexofenadine (36- and 80-fold increase in C_max and AUC at the dose of 24 mg/kg) in rats^[1].