Osilodrostat

产品说明书

Print
Chemical Structure| 928134-65-0 同义名 : LCI699
CAS号 : 928134-65-0
货号 : A151532
分子式 : C13H10FN3
纯度 : 95%
分子量 : 227.24
MDL号 : MFCD25976825
存储条件：

Pure form Sealed in dry, 2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 250 mg/mL(1100.17 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 100 mg/mL(440.07 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：
生物活性
靶点

  • Hydroxylase

    11β-hydroxylase, IC50:2.5 nM
描述 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].
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 24899257
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.40mL

0.88mL

0.44mL

22.00mL

4.40mL

2.20mL

44.01mL

8.80mL

4.40mL
参考文献

[1]Bertagna X, Pivonello R, et al. LCI699, a potent 11β-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing's disease: results from a multicenter, proof-of-concept study. J Clin Endocrinol Metab. 2014 Apr;99(4):1375-83.

[2]Amar L, Azizi M, et al. Aldosterone synthase inhibition with LCI699: a proof-of-concept study in patients with primary aldosteronism. Hypertension. 2010 Nov;56(5):831-8.

[3]Zhu W, Chen Z, Li Q, Tan G, Hu G. Inhibitors of 11β-Hydroxylase (CYP11B1) for Treating Diseases Related to Excess Cortisol. Curr Med Chem. 2016;23(6):623-633.

[4]Bertagna X, Pivonello R, Fleseriu M, et al. LCI699, a potent 11β-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing's disease: results from a multicenter, proof-of-concept study. J Clin Endocrinol Metab. 2014;99(4):1375-1383.

[5]Amar L, Azizi M, Menard J, Peyrard S, Watson C, Plouin PF. Aldosterone synthase inhibition with LCI699: a proof-of-concept study in patients with primary aldosteronism. Hypertension. 2010;56(5):831-838.