Gamitrinib TPP hexafluorophosphate is a mitochondrial-targeted HSP90 inhibitor with anticancer activity, which can regulate cell cycle and cell homeostasis and can be used to study cancer, neurodegenerative diseases and viral infections.

Within a 16-hour exposure, concentrations of G-TPP of 15–20 μM indistinguishably killed patient-derived and cultured glioblastoma cell lines, G-TPP did not kill normal fetal human astrocytes (FHAS). Cell viability measured by MTT. Cultured glioblastoma cell lines (U87; LN229; U251), patient-derived glioblastoma cells (GS620; GS48; AS515), or SV40-transformed normal FHAS. [1]
The “mitochondriotoxic” activity of G-TPP did not involve changes in expression of pro- or antiapoptotic Bcl-2 family proteins or recruitment of Bax to mitochondria. U87 cells were incubated with 0–10 μM G-TPP for 16 hours and analyzed by WB. LN229 cells were treated with or without G-TPP and cytosol (Cyto) or mitochondrial extracts (MTE) and were analyzed after 6 hours by WB. [1]
G-TPP treatment leads to PINK1 stabilization and pS65-Ub induction in HeLa cells. HeLa cells stably expressing untagged Parkin were treated with 10 μM G-TPP. PINK1 protein was undetectable in untreated cells, but accumulated 8 h after treatment with G-TPP along with the increase of pS65-Ub signal by Western blots. [1]

Systemic monotherapy with G-TPP at concentrations (20 mg/kg as daily i.p. injections) that inhibit subcutaneous xenograft tumor growth in mice had no effect on orthotopic glioblastoma growth. Nude mice carrying intracranial U87-Luc glioblastomas were treated. Treatment was suspended on day 10 after tumor implantation, and tumor growth was assessed weekly. [1]
G-TPP treatment leads to PINK1 stabilization and pS65-Ub induction in HeLa cells. HeLa cells stably expressing untagged Parkin were treated with 10 μM G-TPP. PINK1 protein was undetectable in untreated cells, but accumulated 8 h after treatment with G-TPP along with the increase of pS65-Ub signal by Western blots. [2]