CYP11B1-IN-2 (compound 7aa) 是一种口服有效且选择性的CYP11B1抑制剂，其对 human CYP11B1 和 rat CYP11B1 的IC50值分别为 9 nM 和 25 nM。CYP11B1-IN-2 可用于皮质醇过量所致疾病的研究。
| 生物活性 | CYP11B1-IN-2 (compound 7aa) is an orally active, potent and selectiveCYP11B1inhibitor, withIC50values of 9 nM and 25 nM for human CYP11B1 and rat CYP11B1, respectively. CYP11B1-IN-2 can be used for the research of diseases caused by excessive cortisol[1]. |
| IC50& Target | CYP11B1 9 ± 2 nM (IC50, human CYP11B1) | CYP11B1 25 nM (IC50, rat CYP11B1) | CYP11B2 1121 ± 237 nM (IC50) | CYP1A2 >10 μM (IC50) | CYP2C9 >10 μM (IC50) | CYP2C19 >10 μM (IC50) | CYP2D6 >10 μM (IC50) | CYP2E1 >10 μM (IC50) | CYP3A4 >10 μM (IC50) |
|
体外研究
(In Vitro) | CYP11B1-IN-2 (compound 7aa) exhibits good selectivity over a panel of hepatic CYP enzymes, such as CYP1A2, CYP2C9, CYP2C19, CYP3A4, CYP2D6, and CYP2E1 with IC50values greater than 10 μM[1].
CYP11B1-IN-2 presents a cLog P of 3.12, indicating a good balance between lipophilicity and hydrophilicity, which was further manifested by an aqueous solubility of 196 μM[1].
|
体内研究
(In Vivo) | CYP11B1-IN-2 (compound 7aa) (25 mg/kg, Orally, once) reduces plasma cortisol concentrations in rats[1].
CYP11B1-IN-2 (5 mg/kg (IV) or 25 mg/kg (Orally); once) has a maximum plasma concentration of 12 686 μg/L, with similar terminal half-lives of around 4.5 h[1].
| Animal Model: | Adult Sprague-Dawley rats (male, 250-300 g)[1] | | Dosage: | 25 mg/kg | | Administration: | Orally, once | | Result: | Strongly reduced the plasma concentrations of cortisol from 376 ± 22 to 28 ± 5 ng/L after a dose of 25 mg/kg body weight per oral in rats. |
| Animal Model: | Adult Sprague-Dawley rats (male, 250-300 g)[1] | | Dosage: | 5 mg/kg (IV) or 25 mg/kg (Orally) | | Administration: | IV or Orally, once | | Result: | Pharmacokinetic Parameters of CYP11B1-IN-2 in male Sprague-Dawley rats[1].
| IV (5 mg/kg) | PO (25 mg/kg) | | Tmax(h) | 0 | 4.2 ± 0.2 | | Cmax(μg/L) | 12 685.7 ± 421.3 | 7993.3 ± 478.7 | | AUC0-∞(μg/L·h) | 50 928.7 ± 982.6 | 54 539.2 ± 1633.9 | | T1/2(h) | 4.5 ± 0.4 | 4.6 ± 0.2 | | CL (mL/h/kg) | 17.2 ± 1.2 | | | F (%) | | 21.4 |
|
|
m.cnreagent.com