Abstract
BACKGROUND AND OBJECTIVE: CDK7, a member of the CDK-activating kinase (CAK) family, plays a key role in cell cycle, transcriptional regulation and in regulating the proliferation and apoptosis of tumor cells. Some evidence suggests that CDK7 is a promising target for cancer treatments, so it is of great significance to develop an efficient and highly selective CDK7 inhibitor. CDK7 inhibitors have not yet been marketed. This review focuses on some selective CDK7 inhibitors currently in clinical research, and introduces their targets, indications, and the latest clinical trial progress in detail. METHODS: We investigated the recent advances in development of CDK7 inhibitors and their clinical trials from online website (Google Scholar, ClinicalTrials.gov) and electronic databases [PubMed, CDDI (Cortellis Drug Discovery Intelligence)]. KEY CONTENT AND FINDINGS: CDK7, as an important pathway key node, is involved in the regulation and transcription of the cell cycle, and is highly expressed in a variety of tumor cells, which is a good biomarker. In addition, CDK7 plays a key role in regulating the proliferation and apoptosis of tumor cells. By selectively inhibiting CDK7 activity in tumor tissues, it can play a positive role in tumor treatment. Compared with the first-generation pan-CDK7 inhibitors, the second-generation selective CDK7 inhibitors have more potent activity, better selectivity and druggability. Selective CDK7 inhibitors currently under investigation are mainly divided into two categories: (I) selective covalent CDK7 inhibitors and (II) selective non-covalent CDK7 inhibitors. This review summarizes the recent findings on selective CDK7 inhibitors, with a focus on their indications, and the latest clinical trial progress. CONCLUSIONS: Overall, CDK7 is a very promising anti-tumor target for the treatment of breast cancer, solid tumors, ovarian cancer and triple negative breast cancer (TNBC), etc. There is no doubt about that, however, its specific inhibitors still need to be developed with scientists' tireless efforts.