A Dual Inhibitor of Cdc7/Cdk9 Potently Suppresses T Cell Activation

T cell activation is mediated by signaling pathways originating from the T cell receptor (TCR). Propagation of signals downstream of the TCR involves a cascade of numerous Kinases, some of which have yet to be identified. Through a screening strategy that we have previously introduced, PHA-767491, an inhibitor of the Kinases Cdc7 and CDK9, was identified to impede TCR signaling. PHA-767491 suppressed several T cell activation phenomena, including the expression of activation markers, proliferation, and effector functions. We also observed a defect in TCR signaling pathways upon PHA-767491 treatment. Inhibition of CDC7/CDK9 impairs T cell responses, which could potentially be detrimental for the immune response to Tumors, and also compromises the ability to resist infections. The CDC7/CDK9 Inhibitor is a strong candidate as a Cancer therapeutic, but its effect on the immune system poses a problem for clinical applications.