ZYF0033 (HPK1-IN-22, compound ZYF0033) is a hematopoietic progenitor kinase 1 (HPK1) inhibitor with an IC50 less than 10 nM based on the phosphorylation inhibition of MBP protein. ZYF0033 decreases the phosphorylation of SLP76 (serine 376). ZYF0033 promotes anticancer immune responses. ZYF0033 inhibits tumor growth and caused increases intratumoral infiltration of DCs, NK cells, and CD107a+CD8+ T cells but decreased infiltration of regulatory T cells, PD-1+CD8+ T cells, TIM-3+CD8+ T cells, and LAG3+CD8+ T cells in the 4T-1 syngeneic mouse model[1].
[1]. Jingwen Si, et al. Hematopoietic Progenitor Kinase1 (HPK1) Mediates T Cell Dysfunction and Is a Druggable Target for T Cell-Based Immunotherapies. Cancer Cell. 2020 Oct 12;38(4):551-566.e11.