In Silico‐Enabled Discovery and Development of Potent and Selective CDK11 Inhibitors

4 nM, kinome panel clean). In a lung tumour model, mice dosed twice daily with 100 mg/kg of compound 37 showed ∼30% tumour growth inhibition. Both in vitro absorption, distribution, metabolism and excretion and in vivo mouse pharmacokinetics (PK) profiling indicated that compound 37 possesses excellent PK/pharmacodynamic properties, positioning the compound for further development and evaluation as a lead candidate for CDK11-targeted therapy. Meanwhile, the series of compounds developed throughout this study represent novel tools for studying CDK11-mediated pathophysiology. The integration of in silico modelling, screening and structure-based drug design provides a robust strategy for accelerating the identification of potent and selective inhibitors for other CDK families.