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A paper describing the drug discovery research of the CDK12 inhibitor CTX-439 has been published in ACS Medicinal Chemistry Letters
2026.07.07
Discovery of CTX-439: A Potent and Selective CDK12 Inhibitor as a Prospective Anti-Cancer Drug
Publication
Published Date: 2026/6/23
The results of drug discovery research led by Chordia Therapeutics, Inc., have been published online in ACS Medicinal Chemistry Letters, a peer-reviewed journal of the American Chemical Society (ACS).
Paper Summary
This paper describes the discovery of CTX-439, a highly selective inhibitor targeting cyclin-dependent kinase 12 (CDK12), which has attracted attention as a promising new target for cancer therapy. CDK12 is a kinase that regulates key genes, including BRCA1 and BRCA2, involved in transcriptional regulation and DNA damage repair (DDR) pathways. It is considered a promising therapeutic target for tumors harboring BRCA mutations or homologous recombination deficiency (HRD).
In this study, lead optimization starting from a lead compound with a unique scaffold led to the identification of CTX-439, a compound that combines potent inhibitory activity against CDK12 (Kd = 0.38 nM) with more than 550-fold selectivity over other CDK family members. CTX-439 is being further developed by Chordia Therapeutics, Inc. as a candidate anticancer therapeutic.
In this publication, Axcelead contributed to the lead optimization research, particularly in the area of medicinal chemistry. This achievement was made possible through strategic compound optimization leveraging our chemistry and screening platforms with Chordia Therapeutics, Inc..
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Takaharu Hirayama, Project Management, Director
After completing his master’s degree at the Graduate School of Engineering, Kyoto University, Takaharu Hirayama joined Takeda Pharmaceutical Company Limited. During his tenure at Takeda, he earned a doctoral degree from the Graduate School of Kyoto Pharmaceutical University. After joining Axcelead Drug Discovery Partners, Inc. in 2017, he served in a number of leadership roles, including Medicinal Chemistry Team Lead, Computational Chemistry Team Lead, Head of the Chemistry Division, and Head of the Data Science and Informatics Division. He is currently engaged in project management for drug discovery projects. Drawing on his extensive drug discovery experience cultivated in the field of medicinal chemistry, he works closely with clients every day to take on the challenge of co-creating new medicines.