IVMT-Rx-3

IVMT-Rx-3 is a first-in-class, second-generation dual-PDZ domain inhibitor of Melanoma differentiation-associated gene-9 (MDA-9), also known as Syntenin-1 or Syndecan-binding protein (SDCBP). It is a chimeric molecule composed of a small molecule inhibitor of the PDZ1 domain (PDZ1i) conjugated to a PDZ2-selective peptide (TNYYFV) via a PEG linker. By simultaneously engaging both PDZ domains of MDA-9, IVMT-Rx-3 disrupts the interaction between MDA-9 and c-Src, leading to the downregulation of NF-kB activation and subsequent suppression of MMP2 and MMP9. This mechanism inhibits cancer cell invasion and metastasis. Developed by researchers at Virginia Commonwealth University and the University of Pittsburgh, IVMT-Rx-3 has shown efficacy in inhibiting melanoma metastasis in murine syngeneic models and patient-derived cell lines, particularly when combined with immune-checkpoint inhibitors.