Development of the First Small-Molecule Inhibitor Targeting Oncostatin M for Treatment of Breast Cancer.

ABSTRACT: Oncostatin M (OSM) is a proinflammatory cytokine implicated in inflammatory diseases and multiple cancers, especially breast cancer. To date, no federally approved anti-OSM therapeutics exist. We computationally screened ∼1.65 million compounds to identify small-molecule inhibitors (SMIs) of the OSM, and candidates were validated in human breast cancer models. We identified a tetrasubstituted furan (SMI-10) that inhibited OSM signaling, and optimization generated SMI-10B (K_D = 12.9 μM) and SMI-10B13 (K_D = 6.6 μM). SMI-10B13 strongly inhibited OSM-mediated STAT3 phosphorylation in T47D and MCF-7 cell lines (IC₅₀= 136 and 164 nM, respectively). Fluorescence quenching, NMR, and surface plasmon resonance assays were used to ch

SUBMITTER: Wolf CL 

PROVIDER: S-EPMC12362618 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature