Chen, Elijah W. Tay, Neil Q. Brzostek, Joanna Gascoigne, Nicholas R. J. Rybakin, Vasily Image_1_A Dual Inhibitor of Cdc7/Cdk9 Potently Suppresses T Cell Activation.TIFF <p>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.</p> Cdc7;Cdk9;PHA-767491;TCR signaling;T cell activation;thymocyte selection 2019-07-25
    https://frontiersin.figshare.com/articles/figure/Image_1_A_Dual_Inhibitor_of_Cdc7_Cdk9_Potently_Suppresses_T_Cell_Activation_TIFF/9097361
10.3389/fimmu.2019.01718.s001