聚四氟乙烯
癌症研究
细胞周期蛋白依赖激酶9
生物
激酶
蛋白激酶A
遗传学
细胞周期蛋白依赖激酶2
基因
发起人
基因表达
作者
Lanshu Xiao,Yi Liu,Hui Chen,Lisong Shen
标识
DOI:10.1080/15384047.2023.2219470
摘要
As a catalytic subunit of the positive transcription elongation factor b (P-TEFb), cyclin-dependent kinase 9 (CDK9) has been demonstrated to contribute to carcinogenesis. This review focuses on the development of selective CDK9 inhibitors and proteolysis-targeting chimera (PROTAC) degraders. Twenty selective CDK9 inhibitors and degraders are introduced along with their structures, IC50 values, in vitro and in vivo experiments, mechanisms underlying their inhibitory effects, and combination regimens. NVP-2, MC180295, fadraciclib, KB-0742, LZT-106, and 21e have been developed mainly for treating solid tumors, and most of them work only on certain genotypes of solid tumors. Only VIP152 has been proven to benefit the patients with advanced high-grade lymphoma (HGL) and solid tumors in clinical trials. Continued efforts to explore the molecular mechanisms underlying the inhibitory effects, and to identify suitable tumor genotypes and combination treatment strategies, are crucial to demonstrate the efficacy of selective CDK9 inhibitors and degraders in tumor therapy.
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