BAY-405 (BAY405) is a potent, selective MAP4K1 (HPK1) inhibitor with IC50 of 6 nM in binding competition assays.
BAY-405 inhibits SLP76 phosphorylation with submicromolar potency (IC50=0.63 uM) and shows good kinase selectivity.
BAY-405 enhances T-cell immunity and overcomes the suppressive impact of PGE2, TGFβ and CD4+ T-regulatory cells.
BAY-405 demonstrated single-agent efficacy in syngeneic EMT6 breast and B16-OVA melanoma mouse models, as well as benefits when combined with anti-PDL1 Ab in the B16-OVA model.
1. Leder, G. et al. Enhancement of anti-tumor T-cell immunity by means of an oral small molecule targeting the intracellular immune checkpoint MAP4K1. Cancer Res. 81 (Suppl. 13), Abstr. 1722 (2021).
2. Mowat J, et al. J Med Chem. 2024 Sep 27. doi: 10.1021/acs.jmedchem.4c01325.
