TTX01 / Triterpenoid Therap - LARVOL DELTA

The synthetic oleanane triterpenoid CDDO-2P-Im binds GRP78/BiP to induce unfolded protein response-mediated apoptosis in myeloma. (PubMed, Mol Oncol) - "Here we show synergy of 2P-Im and the proteasome inhibitor ixazomib in human multiple myeloma (MM) cells, and 2P-Im activity in a murine model of plasmacytoma. Finally, both drug affinity responsive target stability (DARTS) and thermal shift assays demonstrated direct binding of 2P-Im to endoplasmic reticulum chaperone BiP (GRP78/BiP), a stress-inducible key signaling molecule of the UPR. These data reveal GRP78/BiP as a novel target of SOTs, and specifically of 2P-Im, and suggest the potential broader utility of this class of small molecules as modulators of the UPR."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • DDIT3 • HSPA5 • PERK