Chb-M′, an Inhibitor of the RUNX Family Binding to DNA, Induces Apoptosis in p53-Mutated Non-Small Cell Lung Cancer and Inhibits Tumor Growth and Repopulation In Vivo

Runt-related transcription factor (RUNX) proteins are considered to play various roles in cancer. Here, we evaluated the anticancer activity of Chb-M′, a compound that specifically and covalently binds to the consensus sequence for RUNX family proteins, in p53-mutated non-small cell lung cancer cells. Chb-M′ killed the cancer cells by inducing apoptosis. The compound showed an anticancer effect comparable to that of the clinically used drugs alectinib and ceritinib in vivo. Notably, Chb-M′ extended the cancer-free survival of mice after ending treatment more effectively than did the other two drugs. The results presented here suggest that Chb-M′ is an attractive candidate as an anticancer drug applicable to the treatment of non-small cell lung cancer and various other types of cancers.Runt相关转录因子（RUNX）家族蛋白被认为在癌症进程中发挥多种调控作用。本研究以p53突变型非小细胞肺癌细胞为模型，评估了Chb-M'的抗癌活性——该化合物可特异性共价结合RUNX家族蛋白的保守序列。实验结果表明，Chb-M'通过诱导细胞凋亡实现癌细胞杀伤；体内实验中，其抗癌效果与临床用药阿来替尼（alectinib）、色瑞替尼（ceritinib）相当。值得注意的是，停药后Chb-M'相较于上述两种药物，更能有效延长小鼠的无癌生存期。本研究结果显示，Chb-M'是极具潜力的抗癌候选药物，可用于非小细胞肺癌及多种其他癌症的治疗。