NCIt 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.;
Semantic type(s)