Vicriviroc maleate

A potent, highly selective, and orally bioavailable CCR5 antagonist with Ki of 2.5 nM; display no affinity for muscarinic receptors (Ki>10 uM) ; inhibits HIV-1 entry into U-80 cells with IC50 of 0.8 nM, inhibits HIV-1 clinical isolates in PBMC with IC90 of 1-10 nM; exhibits excellent receptor selectivity and oral bioavailability in rats and monkeys.HIV Infection Phase 3 Clinical (In Vitro) :Vicriviroc maleate (SCH-417690 maleate; SCH-D maleate) is a potent, selective and oral bioavailable inhibitor of CCR5, with a Ki of 2.5 nM, and also inhibits HIV-1 in PBMC cells, with IC90s of 3.3 (JrFL), 2.8 (ADA-M), 1.8 (301657), 4.9 (JV1083) and 10 nM (RU 570) . In addition, Vicriviroc maleate shows a mean IC50 and IC90 of 0.45 nM and 4 nM for a panel of HIV isolates, and has weak activity against hERG activity (IC50, 5.8 μM) . Vicriviroc maleate inhibits chemotactic response to MIP-1α with IC50 values below 1 nM, and suppresses RANTES-induced signaling with a mean IC50 of 4.2 ± 1.3 nM. Vicriviroc maleate potently suppresses all the viral isolates tested, with geometric mean EC50s of 0.04-2.3 nM and IC90s of 0.45-18 nM. (In Vivo) :Vicriviroc maleate (SCH-417690 maleate; SCH-D maleate; 10 mg/kg) has good oral availablity in rats and monkeys, with no acute CNS or GI effects in rats.