CTX-439 is a potent, selective, orally bioavailable, ATP-competitive CDK12/13 inhibitor with IC50 of 3.1/ 9.2 nM towards CDK12/Cyclin K and CDK13/Cyclin K, respectively, in cell-free assays.
CTX-439 possesses a highly specific inhibitory activity towards CDK12/13 compared to other members of the CDK family proteins, showing > 550-fold higher binding affinity and 20-fold higher inhibitory activity than the closest family member, CDK9.
CTX-439 shows high binding affinity towards CDK12 (Kd=0.38 nM).
CTX-439 downregulated p-S2, but neither phosphorylation of S5 (p-S5) nor phosphorylation of S7 (p-S7) in breast cancer cell line SUM149PT, reduced Serine 423 (S423) of CDK12 phosphorylation level in a dose-dependent manner.
CTX-439 possesses profound anti-tumor effects with IC50 of 100.5 nM against SUM149PT in cell-based assay, shows anti-tumor activity against a broad range of breast and ovarian cancer cell lines.
CTX-439 (15-30 mg/kg, p.o.) showed marked in vivo anti-tumor activity in nude mice bearing SUM149PT xenografts.