TAK-700 (Orteronel)

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Orteronel (TAK-700) 是一种高度选择性的人17，20-裂解酶 (17,20-lyase, CYP17) 抑制剂，IC50 值为 38 nM，对其选择性是对 11-hydroxylase 和 CYP3A4 的 1000 多倍。

Orteronel(TAK-700) was selected as a candidate for clinical evaluation. orteronel (TAK-700) is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer.

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. 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.

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. In cynomolgus monkeys, oral treatment of Orteronel at a dose of 1 mg/kg markedly reduces serum testosterone and dehydroepiandrosterone (DHEA) levels.

Orteronel

Metabolic Enzyme/Protease

P450

20-lyase(Rat)| 20-lyase(Human)

Cancer

Prostate Cancer

566939-85-3

307.35

C??H??N?O?

>98% (HPLC)

DMSO:61 mg/mL (198.47 mM); Ethanol:8 mg/mL (26.02 mM);Water:<1 mg/mL

CNC(=O)C1=CC2=C(C=C1)C=C(C=C2)[C@]3(CCN4C3=CN=C4)O

——

(-20℃)

With Ice Pack

≥ 2 years