ZYF0033 is a potent inhibitor of hematopoietic progenitor kinase 1 (HPK1), achieving an IC50 of less than 10 nM by inhibiting the phosphorylation of MBP protein. This compound enhances anti-cancer immune responses, leading to a reduction in serine 376 phosphorylation of SLP76. In preclinical studies with the 4T-1 syngeneic mouse model, ZYF0033 demonstrated significant tumor growth inhibition and increased intratumoral infiltration of dendritic cells, natural killer cells, and CD107a+CD8+ T cells, while decreasing infiltration of various PD-1+ and TIM-3+ CD8+ T cell subsets.
ZYF0033 is a potent inhibitor of hematopoietic progenitor kinase 1 (HPK1), achieving an IC50 of less than 10 nM by inhibiting the phosphorylation of MBP protein. This compound enhances anti-cancer immune responses, leading to a reduction in serine 376 phosphorylation of SLP76. In preclinical studies with the 4T-1 syngeneic mouse model, ZYF0033 demonstrated significant tumor growth inhibition and increased intratumoral infiltration of dendritic cells, natural killer cells, and CD107a+CD8+ T cells, while decreasing infiltration of various PD-1+ and TIM-3+ CD8+ T cell subsets.
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