摘要
肝细胞癌(HCC)是世界上最具侵袭性的实体恶性肿瘤之一,尽管近几十年来在肝切除术、射频消融和肝移植等方面取得了显著进展,但HCC患者的愈后仍不乐观,主要原因是HCC的高复发率和转移率以及该疾病对化疗和靶向治疗的耐受性。VEGFR2和PD-L1抑制剂联合应用能对小鼠体内的HCC肿瘤进行显著抑制并延长其寿命,因此开发VEGFR2与PD-L1双靶点抑制剂对HCC的治疗具有十分重要的意义。本文基于计算机辅助药物设计(CADD),经过以分子对接为基础的虚拟筛选、MM-GBSA和ADMET评价以及QSAR模型预测,得到了一系列VEGFR2和PD-L1的双靶点活性化合物,有望为后续抑制剂的开发提供思路和方向。
Hepatocellular carcinoma(HCC)is one of the most aggressive solid malignancies in the world.Despite significant advances in hepatectomy,radiofrequency ablation and liver transplantation in recent decades,the prognosis for HCC patients remains poor,mainly due to the high rate of HCC recurrence and metastasis,as well as the disease’s tolerance to chemotherapy and targeted therapies.The combination of VEGFR2 and PD-L1 inhibitors can significantly inhibit HCC tumors in mice and extend their lifespan.Therefore,the development of dual target inhibitors of VEGFR2 and PD-L1 is of great significance for the treatment of HCC.Based on computer aided drug design(CADD),a series of dual-target active compounds for VEGFR2 and PD-L1 have been obtained through molecular dock-based virtual screening,MM-GBSA and ADMET evaluation,and QSAR model prediction,which is expected to provide ideas and directions for the development of subsequent inhibitors.
作者
郑伟
童荣生
何俊
师健友
ZHENG Wei;TONG Rongsheng;HE Jun;SHI Jianyou(Department of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611100,China;Department of Pharmacy,Sichuan Academy of Medical Sciences-Sichuan Provincial People’s Hospital,Chengdu 610031,China;State Key Laboratory of Biotherapy of Sichuan University,Chengdu 610041,China)
出处
《合成化学》
CAS
2023年第5期321-328,共8页
Chinese Journal of Synthetic Chemistry
基金
国家自然科学基金资助项目(2073311)。
