活性导向的细胞毒类抗肿瘤中药毒效关联性评价和成药性优化

Evaluation of effectiveness-cytotoxicity correlation and optimization of druggability for activity-based poisonous Chinese materia medica with antitumor activity

来源于具有毒性的中药材的独特成分抗肿瘤效应显著,但因不可预见的毒性使其临床应用的安全性受到质疑。为完善该类药物的成药性,迫切需要加强其抗肿瘤活性和细胞毒效应关联性研究。活性导向的化学蛋白质组学研究能够实现以药物自身活性指导下的中药药理和毒副作用发现以及合理药物设计。同时鉴于中药分子的泛靶点性,利用比较正常与肿瘤细胞靶标谱的生物网络计算方法搜寻潜在的成药性靶标,开展药物结构的优化设计,通过"药→病→靶→药"的回路研究模式,以期为从有毒中药开发出高效、低毒的抗肿瘤新药提供参考。

The antitumor activity of the constituents from poisonous Chinese materia medica（CMM） is very strong,but mainly mediated by their unforeseeable cytotoxic effects,which results in increasingly prominent security issues in clinic.To improve the druggability of these drugs,it is urgent to put much attention on the effectiveness-cytotoxicity correlation study.Activity-based protein profiling can realize the discovery of pharmacological and cytotoxic information and drug design under the guidance of chemicals activity.In view of the promiscuity of natural chemicals,we utilize the method of comparative targets profile to calculate and seek druggable targets in biological networks for drug structure optimization.In conclusion,we take the loop mode of drug→disease→target→drug method,hoping to provide the reference for the research and development of new drug with high efficiency and low toxicity from poisonous CMM.