CTX-439

CTX-439 is an orally active, ATP-competitive small-molecule inhibitor of CDK12 and CDK13, with an IC₅₀ of 3.1 nM and a K d of 0.38 nM against CDK12, and an IC₅₀ of 9.2 nM against CDK13. CTX-439 induces DNA damage and apoptosis in tumor cells. CTX-439 is applicable for the research of breast cancer and ovarian cancer ^[1].

In Vivo, CTX-439 (7.5-30 mg/kg; p.o.; twice weekly; 15 days) inhibits the growth of SUM149PT breast cancer xenografts in nude mice in a dose-dependent manner^[1].

In Vitro, CTX-439 (0-10 μM; 6-72 h) inhibits the proliferation of SUM149PT cells with an IC₅₀ of 100.5 nM, induces DNA damage and apoptosis, and downregulates the expression of DNA damage repair genes by inhibiting CDK12 activity^[1]. CTX-439 (0-1 μM; 0-24 h) downregulates MCL1 protein levels in SUM149PT and OV90 cells^[1]. CTX-439 (100-800 nM; 4-8 h) synergizes with the BCL-2/BCL-xL inhibitor AZD4320 to rapidly induce apoptosis in SUM149PT and OV90 cells^[1].

References:
[1]. Yamakawa H, et al. CDK12/13 inhibitor, CTX-439, suppresses tumor growth and potentiates BCL-2 family blockade. bioRxiv, 2026: 2026.02. 20.706902.