DS21150768 is a potent selective and orally active hematopoietic progenitor kinase 1 (HPK1, MAP4K1) inhibitor with IC50 of 3.27 nM in cell-free HPK1 assays, binds to HPK1 with an affinity constant (KD) of 6.08 nM.
DS21150768 is selective against MAP4K family members HGK (MAP4K4) and MINK (MAP4K6), and cell-free kinase panel assay of 174 kinases.
DS21150768 inhibits the phosphorylation of SLP76 (pSLP76) induced by the stimulation in a concentration-dependent manner (IC50=61.9 nM) in Jurkat cells, induces enhanced TCR signaling and cytokine production in T cells.
DS21150768 (30 mg/kg, orally) induced significant elevation of IFN-γ levels in plasma and spleen, DS21150768 (100 mg/kg, orally) treatment results in significant increases of both IL-2 and IFN-γ in vivo.
DS21150768 monotherapy (100 mg/kg, orally administered once every 2 days) and the combination treatment with anti-PD1 significantly inhibits tumor growth in B16-BL6, CT26.WT, Pan02, and RM-1.