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  • An orally bioavailable inhibitor of the serine/threonine enzyme hematopoietic progenitor kinase-1 (Hpk1; Hpk-1; mitogen-activated protein kinase kinase kinase kinase 1; MAP4K1), with potential immunostimulating and antineoplastic activities. Upon oral administration, Hpk1 inhibitor CFI-402411 targets, binds to and inhibits the activity of Hpk1. This inhibits Hpk1-mediated signaling pathways and inhibits the proliferation of Hpk1-expressing tumor cells. In addition, CFI-402411 prevents Hpk1-mediated immunosuppression by preventing the inhibition of T cell receptors (TCR) signaling and effector T-cells, disrupting abnormal cytokine expression, and abrogating the immunosuppressive tumor microenvironment (TME). This may activate a cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells. Hpk1 is expressed in hematopoietic cells and a negative regulator of TCR and T- and B-cell activation.
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