W035 + W038

W035 + W038 are two lead functionalized β-lactam-based small molecules identified through diversity-oriented synthesis for the treatment of cutaneous melanoma. These compounds exhibit a multi-target mechanism of action, simultaneously inhibiting the MAPK, PI3K, and JAK/STAT signaling pathways, which are frequently dysregulated in melanoma. In preclinical studies, W035 and W038 demonstrated potent cytotoxicity against human (A375, SK-MEL-28) and murine (B16F10) melanoma cell lines, significantly reduced colony formation and cell migration, and induced apoptosis via caspase-3/7 activation and disruption of redox homeostasis. ADME profiling suggests favorable drug-likeness, including high skin permeability and gastrointestinal absorption, supporting their potential for both topical and systemic administration.