SONIDEGIB PHOSPHATE Smoothened (SMO) receptor antagonist Oncolytic

Sonidegib phosphate (LDE-225) is a potent, orally bioavailable, selective inhibitor of smoothened protein, a key downstream transducer of the hedgehog signaling pathway. This pathway has been recently associated with cancer development and progression in several tumor types, and components of this pathway have been regarded as targets for the development of new anticancer agents. In preclinical studies, sonidegib bound to smoothened protein with high affinity, leading to dose-related inhibition of hedgehog signaling, ultimately resulting in tumor growth arrest and regression. In early clinical studies, sonidegib showed a favorable safety profile and demonstrated promising antitumor activity, mainly in basal cell carcinoma and medulloblastoma. Ongoing trials are evaluating sonidegib either alone in selected cancer types or in combination with conventional cytotoxic drugs against a broad range of solid tumors.