RDP-02004 / RDP Pharma - LARVOL DELTA

Small-molecule stabilization of non-native c-Myc multimer drives degradation using an IDP-targeting discovery platform (AACR 2026) - "Our hit RDP-02004 induced rapid, dose-dependent loss of c-Myc protein (DC₅₀ ~5-10 µM) and apoptosis across diverse MYC-dependent cancer cell lines, including multiple myeloma, lung and triple-negative breast cancer, with selectivity over non-transformed cells...The proteasome inhibitor MG-132, the ubiquitin-activating enzyme inhibitor TAK-243, and the autophagy inhibitor Autophinib each rescued c-Myc levels after compound treatment, implicating both ubiquitin-proteasome and aggrephagy-like mechanisms...Structure-activity and pharmacophore analyses, together with structure-based design, yielded additional series with improved properties and activity (DC₅₀ < 1 µM). These data provide proof of concept that exploiting IDP conformational ensembles to stabilize degradable c-Myc assemblies can generate small-molecule c-Myc degraders and support further optimization of this platform toward safer, more selective anti-MYC therapeutics."

Breast Cancer • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor • Triple Negative Breast Cancer • MYC • SDC1