PF-07265028

PF-07265028 is an HPK1 inhibitor with an IC50 of 17 nM. Pharmacokinetic studies in mice and monkeys indicate that PF-07265028 exhibits moderate clearance, terminal half-life, volume of distribution, and oral bioavailability. It targets, binds, and inhibits Hpk1 activity, blocking Hpk1-mediated signaling pathways to prevent immune suppression mediated by Hpk1, including the inhibition of T-cell receptor (TCR) signaling, effector T-cell suppression, aberrant cytokine expression, and the elimination of the immunosuppressive tumor microenvironment (TME) . This action can activate a cytotoxic T lymphocyte (CTL) -mediated immune response against tumor cells. Hpk1 is primarily expressed in hematopoietic cells and acts as a negative regulator of TCR signaling and T and B cell activation.