Characterization of small molecule inhibitors against Lipocalin-2 in inflammatory breast cancer

Inflammatory breast cancer (IBC) is a rare and very aggressive form of breast cancer (BC) where cancer cells block the lymph vessels in the skin. It only makes up about 1% to 5% of all breast cancers but grows and spreads much faster than other common BC types. No targeted therapies are currently available against IBC. Lipocalin 2 (LCN2) is a secreted glycoprotein involved in transporting small lipophilic ligands, and its abnormal expression plays an important role in the progression and metastasis of IBC. We used a library of 370,000 small molecule inhibitors (SMI) and after bioinformatic and filtering analysis we selected 24 compounds that potentially bind to LCN2. Viability and colony formation assay were performed on the IBC cell line, SUM-149. The majority of the 24 SMIs did not exhibited noticeable reduction on cell viability. However, at 1.0 µM, 12 SMIs achieved >50% reduction in cell proliferation. These results highlight the therapeutic potential and selectivity of SMIs against LCN2. Targeting this protein with our SMIs could provide a novel therapeutic strategy that improves the outcomes of IBC patients. Further studies are needed to validate and optimize the most effective compounds for future clinical development.