Abstract
Hematopoietic progenitor kinase 1 (HPK1), a hematopoietic cell-restricted member of the serine/threonine Ste20-related protein kinases, is a negative regulator of the Tcell receptor, B cell receptor, and dendritic cells. Loss of HPK1 kinase function increases cytokine secretion and enhances Tcell signaling, virus clearance, and tumor growth inhibition. Therefore, HPK1 is considered a promising target for tumor immunotherapy. Several HPK1 inhibitors have been reported to regulate Tcell function. In addition, HPK1-targeting PROTACs, which can induce the degradation of HPK1, have also been developed. Here, we provide an overview of research concerning HPK1 protein structure, function, and inhibitors and propose perspectives and insights for the future development of agents targeting HPK1.
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