KX2-391 dihydrochloride

KX2-391 dihydrochloride（CAS 号 1038395-65-1）是具有多靶点双机制的小分子抑制剂，核心生物活性包括抑制 Src 激酶、微管蛋白聚合、乙肝病毒（HBV）转录及肉毒杆菌神经毒素 A（BoNT/A）活性，作用靶点为 Src 激酶底物结合位点、α-β 微管蛋白异二聚体新结合位点、HBV 前核心启动子及 BoNT/A 轻链（LC）；IC50/GI50 方面，Src 激酶抑制在 NIH3T3/c-Src527F 细胞为 23 nM、SYF/c-Src527F 细胞为 39 nM，微管蛋白聚合抑制细胞内需≥80 nM，抗 HBV EC50 为 PXB 细胞 0.14 μM、HepG2-NTCP 细胞 2.7 μM，抗 BoNT/A 在 10-40 μM 浓度下可抑制 SNAP-25 cleavage；常用应用浓度：体外细胞实验（抗癌 / 抗 HBV）0.013-10 μM，抗 BoNT/A 10-40 μM，动物实验小鼠口服 5-15 mg/kg（每日 1-2 次）、黑猩猩抗 HBV 1 mg/kg 每日两次，临床外用 1% 软膏（10 mg/g）、口服肿瘤治疗 40-120 mg / 天；有效治疗浓度：光化性角化病外用 1% 软膏（每日 1 次连用 5 天），肿瘤口服维持血浆峰浓度 61-218 ng/mL，抗 HBV 需血浆浓度≥560 nM（241.92 ng/mL），其选择性指数抗 HBV 时 PXB 细胞 450、HepG2-NTCP 细胞 > 37，临床耐受性良好，无明显周围神经病变。

参考文献：

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