Discovery of\nA‑910, a Highly Potent and Orally\nBioavailable Dual MerTK/Axl-Selective Tyrosine Kinase Inhibitor

TAM receptor tyrosine kinases have emerged as promising\ntherapeutic\ntargets for cancer treatment due to their roles in both tumor intrinsic\nsurvival mechanisms and suppression of antitumor immunity within the\ntumor microenvironment. Inhibiting MerTK and Axl selectively is believed\nto hinder cancer cell survival, reverse the protumor myeloid phenotype,\nand suppress efferocytosis, thereby eliciting an antitumor immune\nresponse. In this study, we present the discovery of <b>A-910</b>, a highly potent and selective dual MerTK/Axl inhibitor, achieved\nthrough a structure-based medicinal chemistry campaign. The lead compound\nexhibits favorable oral bioavailability, exceptional kinome selectivity,\nand significantly improved in vivo target engagement. These findings\nsupport the use of <b>A-910</b> as an orally bioavailable in\nvivo tool compound for investigating the immunotherapy potential of\ndual MerTK/Axl inhibition.