MD2-IN-1

MD2-IN-1 (CAS No.: 111797-22-9) is a small-molecule chalcone-derived inhibitor of myeloid differentiation protein 2 (MD2), a critical co-receptor for Toll-like receptor 4 (TLR4) that mediates lipopolysaccharide (LPS)-induced innate immune signaling. It directly interferes with the MD2–LPS interaction, exhibiting binding to recombinant human MD2 with a dissociation constant in the micromolar range and effectively reducing LPS association with cell surface MD2 in a dose-dependent manner. Functionally, MD2-IN-1 suppresses downstream TLR4 signaling cascades, including inhibition of NF-κB activation and consequent attenuation of pro-inflammatory cytokine production such as TNF-α and IL-6 in macrophage models, with activity observed at low micromolar concentrations. In cellular and biochemical assays, it demonstrates anti-inflammatory efficacy as well as antiproliferative effects across multiple human cancer cell lines, indicating broader utility in inflammation-associated oncology research. In vivo, MD2-IN-1 has been shown to mitigate LPS-induced acute lung injury, reducing pulmonary edema, inflammatory cell infiltration, bronchoalveolar lavage fluid protein accumulation, and histopathological damage, supporting its role as a pharmacological probe for studying TLR4/MD2-mediated inflammatory disorders. This compound is widely applied in studies of innate immune signaling, cytokine regulation, and preclinical evaluation of anti-inflammatory or anticancer strategies, with experimental concentrations and dosing regimens varying depending on specific model systems and study objectives.