hCYP3A4-IN-1 (compound C6) is a potent, orally active inhibitor of hCYP3A4, exhibiting IC50 values of 43.93 nM in human liver microsomes (HLMs) and 153.00 nM in the CHO-3A4 stably transfected cell line. It competitively inhibits the CYP3A4-mediated hydroxylation of N-ethyl-1,8-naphthalimide (NEN) with a Ki of 30.00 nM [1].

CYP3A4:43.93 nM

hCYP3A4-IN-1（化合物C6）在HLM中显示出了适宜的代谢稳定性，同时在小鼠体内具备良好的安全性 [1]。通过口服一次性给予hCYP3A4-IN-1（100 mg/kg），能够显著提高与midazolam（灌胃，10 mg/kg）联用时的AUC (0-inf) 值，达到原来的3.63倍，并显著延长其在小鼠体内的半衰期，比溶剂组延长了1.66倍 [1]。在小鼠中hCYP3A4-IN-1的药动学参数显示 [1]，与CMC-Na和midazolam联用时，25 mg/kg剂量下T max (分钟)为8.00 ± 2.74，C max (ng/mL)为194.20 ± 138.88，AUC 0-24 (ng/mL∗min)为7520.83 ± 2413.78，t 1/2 (分钟)为36.33 ± 14.46；而100 mg/kg剂量下T max (分钟)为10.00 ± 0.00，C max (ng/mL)为494.67 ± 210.22，AUC 0-24 (ng/mL∗min)为27330.95 ± 6664.85，t 1/2 (分钟)为60.37 ± 27.67。