Cyclin-dependent kinase 12（CDK12）属于丝氨酸/苏氨酸蛋白激酶CDK家族，与环蛋白K相关联以发挥其生物功能，包括调节基因转录、mRNA处理和转化。越来越多的证据表明CDK12在各种人类癌症中的重要性，说明其作为生物标志物和治疗靶标的潜力。此外，CDK12还是治疗型肌阻滞性肌营养不良1型的有希望的靶点。人们已经努力寻找小分子抑制剂以验证这个重要的治疗靶标。本文综述2016年至今已经获得专利的CDK12抑制剂以及来自同行评审的文献。它向读者提供了有关发现策略、化学结构和所有可用CDK12抑制剂的分子特征的最新信息。已经发现了具有不同作用机制的CDK12抑制剂，它是在不同疾病模型中评估CDK12治疗潜力的一组伟大工具。CDK12抑制剂在治疗型肌阻滞性肌营养不良1型小鼠模型和多种临床前癌症模型中，单独或与其他抗癌药物联合使用，均显示出有希望的结果。它的治疗价值需要更加严格的临床前测试和进一步的临床研究。

Cyclin-dependent kinase 12 (CDK12) belongs to the CDK family of serine/threonine protein kinases and is associated with cyclin K to exert its biological functions, including regulating gene transcription, mRNA processing, and translation. Increasing evidences demonstrate the importance of CDK12 in various human cancers, illustrating its potential as both biomarker and therapeutic target. In addition, CDK12 is also a promising target for the treatment of myotonic dystrophy type 1. Efforts have been taken to discover small molecule inhibitors to validate this important therapeutic target.This review covers the patented CDK12 inhibitors from 2016 to present, as well as these from peer-reviewed literature. It provides the reader an update of the discovery strategies, chemical structures, and molecular profiling of all available CDK12 inhibitors.CDK12 inhibitors with various mechanism of actions have been discovered, and it is a great set of tools to evaluate the therapeutic potential of CDK12 in different disease models. CDK12 inhibitors have shown promising results in myotonic dystrophy type 1 mouse model and several preclinical cancer models either as single agent or combination with other anti-cancer agents. Its therapeutic value awaits more rigorous preclinical testing and further clinical investigation.