TAK-700 (Orteronel)是一种有效的，高度选择性的，人17，20-lyase抑制剂，IC50为38 nM，比作用于其他CYPs(例如11-羟化酶和CYP3A4)选择性高1000倍以上。Phase 3。
In vitro, TAK-700 shows the potent inhibitory activity against rat and human steroid 17,20-lyase inhibitor with IC50 of 54 nM and 38 nM, respectively. While other CYP isoforms including 11-hydroxylase and CYP3A4 are not significantly affected by TAK-700. In microsomes expressing human CYP isoforms, TAK-700 exhibit greater inhibitory effects on 17,20-lyase with IC50 of 19 nM compared to the other CYP isoforms. TAK-700 shows the inhibitory activity against monkey 17,20-lyase and 17-hydroxylase with IC50 of 27 nM and 38 nM, respectively. In monkey adrenal cells, TAK-700 inhibits the ACTH stimulated production of DHEA and androstenedione with IC50 of 110 nM and 130 nM, respectively. Moreover, TAK-700 also potently inhibits DHEA production in human adrenocortical tumor line H295R cells with IC50 of 37 nM.
In cynomolgus monkeys, oral treatment of TAK-700 at a dose of 1 mg/kg markedly reduces serum testosterone and dehydroepiandrosterone (DHEA) levels. Oral treatment of TAK-700 at a dose of 1 mg/kg results in favorable pharmacokinetic parameters with T
max, C
max, t
1/2 and AUC
0-24 hours of 1.7 hours, 0.147 μg/mL, 3.8 hours and 0.727 μg h/mL, respectively.
TAK-700 (Orteronel) 是一种有效的，高度选择性的，人17，20-lyase抑制剂，IC50为38 nM，比作用于其他CYPs(例如11-羟化酶和CYP3A4)选择性高1000倍以上。TAK-700 (Orteronel) 是一种雄性激素 androgen 生物合成抑制剂。Phase 3。
| Target | Value |
|
17,20-lyase (Human)
|
38 nM
|
|
17,20-lyase (Rat)
|
54 nM
|
在体外，TAK-700对大鼠和人类固醇17,20-裂解酶表现出有效的抑制活性，IC50分别为54 nM 和38 nM。而其他CYP亚型，包括11-羟化酶和CYP3A4不会被TAK-700显著影响。在表达人CYP亚型的微粒体中，TAK-700对17,20-裂解酶比对其他CYP亚型具有更高的抑制作用，IC50为19 nM。 TAK-700对猴子17,20-裂解酶和17-羟化酶表现出抑制活性，IC50 分别为27 nM和38 nM。在猴子肾上腺细胞中，TAK-700抑制ACTH刺激的DHEA和雄烯二酮产生，IC50 分别为110 nM和130 nM。此外，TAK-700也能有效抑制人肾上腺皮质肿瘤系H295R细胞中DHEA的产生，IC50为37 nM。
在食蟹猴体内，TAK-700(1 mg/kg剂量)口服治疗显著减少血清睾酮和脱氢表雄酮(DHEA)水平。TAK-700(1 mg/kg剂量)口服治疗具有良好的动力学参数，T
max
，C
max
，t
1/2
和AUC
0-24 hours
分别为1.7小时，0.147 μg/mL，3.8 小时和0.727 μg h/mL。
