Definition

A resorcinolic-based mitochondrial-targeted heat shock protein 90 (Hsp90) family inhibitor, with potential antineoplastic activity. Upon administration, gamitrinib targets and inhibits the activity of Hsp90 heat shock proteins, such as TNF receptor-associated protein-1 (TRAP1). This induces the accumulation of the mitochondrial kinase PINK1 and the cytosolic E3 ubiquitin (Ub) ligase Parkin, ubiquitylates substrate proteins, and induces PINK1/Parkin-dependent mitophagy. Gamitrinib induces acute mitochondrial dysfunction, loss of membrane potential and membrane rupture leading to the induction of apoptosis in susceptible tumor cells. Hsp90, a chaperone complex protein upregulated in a variety of tumor cell types, regulates the folding and degradation of many oncogenic signaling proteins.