LY2940680 is a potent and selective antagonist of the hedgehog signaling pathway, primarily targeting the Smoothened (SMO) receptor. It has been investigated for its potential in treating cancers that rely on aberrant hedgehog pathway activation. This includes basal cell carcinoma and certain types of medulloblastoma, where uncontrolled signaling contributes to tumor growth and progression. Due to its ability to cross the blood-brain barrier, LY2940680 shows particular promise in treating central nervous system tumors driven by hedgehog signaling. In preclinical studies, it demonstrated strong antitumor activity, including tumor regression and prolonged survival in animal models. Its selectivity helps reduce off-target effects, potentially improving safety compared to earlier hedgehog inhibitors. LY2940680 has also been explored in combination therapies, where it enhances the efficacy of other anticancer agents such as chemotherapy or targeted drugs. Clinical trials have evaluated its use both as a monotherapy and in combination regimens, aiming to overcome resistance mechanisms seen with other SMO inhibitors. Its development highlights a strategic approach to targeting pathway-dependent malignancies with improved pharmacokinetic and resistance profiles.