metformin + nelfinavir + bortezomib

This combination therapy, investigated by the Mayo Clinic in a Phase 1 trial (NCT03829020), consists of the repurposed drugs metformin and nelfinavir administered alongside the proteasome inhibitor bortezomib for the treatment of relapsed or refractory multiple myeloma. Metformin, a biguanide typically used for type 2 diabetes, acts by disrupting the mitochondrial electron transport chain and inhibiting complex I, which impacts cellular energy metabolism. Nelfinavir, an HIV protease inhibitor, is included for its ability to inhibit glucose transporters (specifically GLUT4) and induce endoplasmic reticulum stress, thereby sensitizing myeloma cells to proteasome inhibition. Bortezomib is a standard-of-care proteasome inhibitor. The triple combination aims to disrupt the Warburg effect and overcome bortezomib resistance by targeting the metabolic vulnerabilities of multiple myeloma cells.

Other names

Metformin and Nelfinavir with BortezomibMetformin Hydrochloride + Nelfinavir Mesylate + Bortezomib