On May 17, 2023, TYK Medicines stated that the Center for Drug Evaluation (CDE) has granted permission for the independently developed next-generation Cyclin-dependent kinase7 (CDK7) inhibitor TY-2699a for clinical trials to be conducted in China.

TY-2699a is China’s first CDK7 inhibitor to be synchronously approved for clinical studies by the CDE and the FDA. Currently, no approved CDK7 inhibitors are on the market, leaving a significant clinical demand unmet.

The picture is from Center for Drug Evaluation of China National Medical Products Administration

About TY-2699a

TY-2699a is a novel, highly effective, and selective small-molecule inhibitor of CDK7, independently developed by TYK Medicines, Inc, aiming for various advanced tumors, such as breast cancer, ovarian cancer, and prostate cancer etc. TY-2699a has demonstrated the marked sensitivity of many cancer types to selective CDK7 inhibition via preclinical animal models, as well as high tolerance and safety, laying a solid foundation for future clinical practice. In addition, TY-2699a showed great performance in breast cancer models with acquired resistance to CDK4/6 inhibitors, implying that TY-2699a may be a viable choice for dealing with drug resistance following CDK4/6 targeted therapy.

About CDK7

CDK7 is a member of the cyclin-dependent kinases (CDK) family and a subunit of the multi-protein transcription factor, TFIIH, playing key roles in both transcription and regulation of the cell cycle. In the cell cycle, CDK7 forms the CDK-activating kinase (CAK) with cyclin H and MAT1 and controls cell cycle progression, particularly in malignant cells, by activating other CDK family kinases (CDK1/2/4/6). Concerning transcription, the CAK module is a component of TFIIH which is a multi-protein complex and is essential for transcription and regulation. CDK7 has been implicated in multiple tumor types driven by aberrant transcriptional control (e.g., MYC-, ESR1-activation) and/or aberrant cell cycle control (e.g., RB1, CCNE1, CDKN2A alterations). Multiple tumors, including but not limited to triple-negative breast cancer (TNBC), relapsed or refractory ovarian cancer (OC), pancreatic ductal adenocarcinoma (PDAC), and blood cancers, have been demonstrated to be highly dependent on CDK7. CDK7 inhibitors are expected to be a promising treatment for such cancers.

References

[1] Suski JM, Braun M, Strmiska V, Sicinski P. Targeting cell-cycle machinery in cancer. Cancer Cell. 2021;39(6):759-778. doi:10.1016/j.ccell.2021.03.010