HCI-2084

HCI-2084 is a small molecule inhibitor of the TAM (Tyro3, Axl, Mer) family of receptor tyrosine kinases, with primary potency against Axl (IC50 = 12 nM). Developed through a collaboration involving the Huntsman Cancer Institute and Tolero Pharmaceuticals, it was designed to target the Axl/Gas6 signaling axis, which is frequently overexpressed in pancreatic cancer and associated with poor prognosis. Mechanistically, HCI-2084 inhibits Axl autophosphorylation and downstream PI3K/Akt signaling, leading to the suppression of epithelial-mesenchymal transition (EMT), inhibition of cell migration and invasion, and induction of apoptosis. In preclinical models, the compound has demonstrated significant growth inhibition of pancreatic cancer cell lines in vitro and in xenograft mouse models.