LP-182

LP-182 is an orally bioavailable, small-molecule, single-entity multi-targeted kinase inhibitor rationally designed to inhibit key nodes in the PI3K and MAPK signaling pathways, including PI3K, mTOR, MEK, and RAF kinases, with high selectivity across a broad kinome panel. Its bulk chemical structure is intrinsically active and engineered to favor lymphatic absorption following oral dosing, leading to sequestration in the mesenteric lymphatic system, prolonged systemic exposure to LP-182 and its active metabolites, and reduced overt toxicity compared with conventional formulations. In preclinical models of myelofibrosis driven by MPL W515L, LP-182 attenuates AKT and ERK1/2 signaling, reduces splenomegaly and bone marrow fibrosis, normalizes blood cell populations, and extends survival, highlighting its potential as a lymphatropic targeted therapy for hematologic malignancies involving dysregulated PI3K/MAPK signaling.[2]