Urea, N-[trans-4-[(5-cyano-2-pyridinyl)amino]cyclohexyl]-N-[4-(1,6-dihydro-1-methyl-6-oxo-3-pyridinyl)phenyl]-N'-(phenylmethyl)-

Uses

CDK12-IN-2 is a potent, selective and nanomolar CDK12 inhibitor (IC50=52 nM) with good physicochemical properties. CDK12-IN-2 is also a strong CDK13 inhibitor due to CDK13 is the closest homologue of CDK12. CDK12-IN-2 shows excellent kinase selectivity for CDK12 over CDK2, 9, 8, and 7. CDK12-IN-2 inhibits the phosphorylation of Ser2 in the C-terminal domain of RNA polymerase II. CDK12-IN-2 can be used an excellent chemical probe for functional studies of CDK12[1].

IC 50

CDK12: 52 nM (IC₅₀); CDK2: >100 μM (IC₅₀); CDK7: >10 μM (IC₅₀); CDK9: 16 μM (IC₅₀)

References

[1] Masahiro Ito, et al. Discovery of 3-Benzyl-1-( trans-4-((5-cyanopyridin-2-yl)amino)cyclohexyl)-1-arylurea Derivatives as Novel and Selective Cyclin-Dependent Kinase 12 (CDK12) Inhibitors. J Med Chem. 2018 Sep 13;61(17):7710-7728. DOI:10.1021/acs.jmedchem.8b00683