TNIK小分子抑制剂在抗肿瘤治疗中的研究进展

Research progress on small-molecule inhibitors targeting TNIK in cancer treatment

肿瘤坏死因子受体相关因子-2和Nck相互作用蛋白激酶(TNIK)与肿瘤的发生、发展和预后密切关系,参与了Wnt/β-catenin等重要的信号通路的调节,是肿瘤治疗中的一个潜在的重要靶标。目前已经报道多种结构多样且体外酶活很高的TNIK抑制剂,但是由于选择性差、毒性大和体内抗肿瘤治疗效果不显著等多方面原因,限制了其进一步开发。截至目前,尚没有一个TNIK抑制剂进入临床研究。本文将对近年来靶向TNIK的小分子抑制剂在抗肿瘤治疗中的最新研究进展进行综述,以期为后续TNIK抑制剂的研究开发提供借鉴。

Traf2-and Nck-interacting kinase(TNIK) is closely related to the cancer occurrence,development,and prognosis.TNIK plays an important role in regulating Wnt/β-catenin pathway,thus becoming a potential target for cancer treatment.Various small-molecule TNIK inhibitors with diverse structures and potent in vitro activities have been developed to treat tumors.However,no TNIK inhibitor has entered clinical phase mainly due to poor selectivity,toxicity,and unsatisfied in vivo anti-tumor efficiency.This review summarizes the research progress of small molecule inhibitors targeting TNIK,with the aim of giving some guidance for future research and development of small-molecule inhibitors.