The overproduction of cortisol is associated with many severe and life-threatening diseases, such as Cushing's syndrome (CS) and chronic wound healing. 11β-Hydroxylase (CYP11B1) is considered as an attractive target for treating these diseases, since it is a key enzyme responsible for the last step in cortisol biosynthesis[3]. LCI699 is a potent inhibitor of 11β-hydroxylase with a half-life of ∼4 hours and an IC50 value of 2.5 nM. Besides CYP11B1, LCI699 can also inhibit aldosterone synthase (CYP11B2). Lower doses of LCI699 (0.25–2 mg/d) decreased aldosterone, inhibited ACTH-induced cortisol stimulation, and increased 11-deoxycorticosterone levels in patients with essential hypertension and primary aldosteronism. Testosterone levels increased significantly in the female patients with Cushing's syndrome who received LCI699, from a baseline mean of 28.8 to 60.5 ng/dL by day 56[4]. In patients with primary aldosteronism, the supine plasma aldosterone concentration decreased from 540 pM (95% CI: 394 to 739 pM) to 171 pmol/L (95% CI: 128 to 230 pM) after 0.5 mg of LCI699 (-68%; P<0.0001) and to 133 pM (95% CI: 100 to 177 pM) after 1.0 mg of LCI699 (-75%; P<0.0001)[5].
Osilodrostat/奥西卓司他 细胞研究
细胞系
浓度
检测类型
检测时间
活性说明
数据源
NCI-H295R cells
Function assay
Inhibition of CYP11B2 in human NCI-H295R cells assessed as inhibition of angiotensin-2-induced aldosterone production after 24 hrs by RIA, IC50=9 nM
24900631
renal leiomyoblastoma cells
Function assay
Inhibition of mouse CYP11B2 expressed in renal leiomyoblastoma cells, IC50=0.21 μM
26403853
V79MZh cells
Function assay
Inhibition of human CYP11B2 expressed in hamster V79MZh cells using deoxycorticosterone as substrate, IC50=0.2 nM
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