PDZ1i is a small molecule developed by InVaMet Therapeutics (IVMT) through NMR-guided fragment-based drug design that is an effective inhibitor of the ultimate and most lethal stage of cancer progression, metastasis. This novel first-in-class small molecule inhibitor binds specifically to the PDZ1 domain of the pro-metastatic gene, MDA-9/Syntenin, blocking essential protein-protein interactions regulating essential cancer signaling properties. Based on the relevance of MDA-9/Syntenin to cancer development, metastasis, and patient-survival, as well as the broad-spectrum anti-cancer activity of the PDZ1i drug, bringing this lead agent into the clinic is a primary objective of IVMT.

• PDZ1i has shown profound “anti-invasive” and “anti-metastatic” activity in multiple cancers, including melanoma, GBM, neuroblastoma and carcinomas of the breast, liver, lung, pancreas and prostate. PDZ1i inhibits retention of tumor cells in the lungs, restricts lung metastasis formation, suppresses breast and prostate metastases, blocks metastatic cancer cell attachment and dissemination and inhibits invasion, thereby prolonging survival following xenograft implantation into nude mice. Additionally, when combined with other modes of therapy, including chemotherapy, radiotherapy and immunotherapy, therapeutic outcomes are significantly enhanced.
• Although not cytotoxic to cancer or normal cells alone, when PDZ1i is combined with currently used therapeutic treatments (including chemotherapy, radiation therapy or immunotherapy), “anti-invasion therapy” is converted to “cytotoxic therapy”.