2020052-55-3

CDK12-IN-E9 is a covalent inhibitor of CDK12. It has been shown to overcome resistance to the THZ series of covalent transcriptional CDK Inhibitors.

CDK12-IN-E9 is a potent and selective covalent CDK12 inhibitor and a non-covalent CDK9 inhibitor, while avoiding ABC transporter-mediated efflux. CDK12-IN-E9 has weak binding ability to CDK7/CyclinH complex with an IC50> 1 μM[1].

CDK12; CDK9/cyclinT1: 23.9 nM (IC₅₀); cdk2/cyclin A: 932 nM (IC₅₀); CDK7/Cyclin H/MNAT1: 1210 nM (IC₅₀)

[1] Gao Y, et al. Overcoming Resistance to the THZ Series of Covalent Transcriptional CDK Inhibitors. Cell Chem Biol. 2018 Feb 15;25(2):135-142.e5. DOI:10.1016/j.chembiol.2017.11.007