CDK12/13-IN-3 (Compound 12b) is the orally active inhibitor for CDK that inhibits CDK12 and CDK13 with IC50 of 107.4 nM and 79.4 nM. CDK12/13-IN-3 inhibits the phosphorylation of Ser2 on the CTD of RNA polymerase II, induces DNA damage, and downregulates the gene expression of DNA damage response (DDR). CDK12/13-IN-3 exhibits antiproliferative activity against multiple cancer cells with IC50 of nanomolar levels. CDK12/13-IN-3 exhibits antitumor effect in mouse models, exhibits good pharmacokinetic properties with an oral bioavailability of 53.6% [1].
References:
[1]. Lu H, et al., Design, Synthesis, and Biological Evaluation of Novel Orally Available Covalent CDK12/13 Dual Inhibitors for the Treatment of Tumors. J Med Chem. 2025 Feb 27;68(4):4148-4167.
References:
[1]. Lu H, et al., Design, Synthesis, and Biological Evaluation of Novel Orally Available Covalent CDK12/13 Dual Inhibitors for the Treatment of Tumors. J Med Chem. 2025 Feb 27;68(4):4148-4167.