tcsc0580 Orteronel

Orteronel is a highly selective inhibitor of human 17,20-lyase with IC₅₀ of 38 nM, and exhibits >1000-fold selectivity over other CYPs such as 11-hydroxylase and CYP3A4.

IC50 & Target: IC50: 38 nM (human 17,20-lyase), 54 nM (rat 17,20-lyase)

In Vitro: In monkey adrenal cells, orteronel inhibits the ACTH stimulated production of DHEA and androstenedione with IC₅₀ of 110 nM and 130 nM, respectively. Moreover, Orteronel also potently inhibits DHEA production in human adrenocortical tumor line H295R cells with IC₅₀ of 37 nM^[1]. In vitro, orteronel shows the potent inhibitory activity against rat and human steroid 17,20-lyase with IC₅₀ of 54 nM and 38 nM, respectively. While other CYP isoforms including 11-hydroxylase and CYP3A4 are not significantly affected by Orteronel. In microsomes expressing human CYP isoforms, Orteronel exhibit greater inhibitory effects on 17,20-lyase with IC₅₀ of 19 nM compared to the other CYP isoforms^[2].

In Vivo: Orteronel (1 mg/kg, p.o.) results in favorable pharmacokinetic parameters with Tmax, Cmax, t1/2 and AUC0-24 hours of 1.7 hours, 0.147 μg/mL, 3.8 hours and 0.727 μg/mL, respectively^[1]. In cynomolgus monkeys, oral treatment of Orteronel at a dose of 1 mg/kg markedly reduces serum testosterone and dehydroepiandrosterone (DHEA) levels^[2].