JMC14

JMC14 is a novel, orally bioavailable small molecule that acts as a dual inhibitor of PI3Kδ (phosphoinositide 3-kinase delta) and CSF1R (colony-stimulating factor 1 receptor). It demonstrates high selectivity within the human kinome, with IC50 values of 12 nM for PI3Kδ and 143 nM for CSF1R. JMC14 preferentially inhibits PI3Kδ-mediated signaling in immune cells and shows robust antiproliferative activity against diffuse large B-cell lymphoma (DLBCL) cell lines, outperforming the approved PI3Kδ inhibitor idelalisib. In preclinical models, it also suppresses tumor progression in xenografts derived from DLBCL patients and TMD8 cells with good tolerance. Additionally, JMC14 effectively inhibits M-NFS-60 myeloid leukemia cells dependent on the CSF-1-CSF1R axis and demonstrates potent antitumor activity in murine triple-negative breast cancer by reshaping the immune microenvironment—reducing M2-like tumor-associated macrophages (TAMs) and enhancing CD8+ T cell infiltration. These findings highlight its potential utility against both hematologic malignancies (such as B-cell cancers) and solid tumors characterized by hyperactivation of PI3Kδ or CSF1R[1][3].