Related Experiment Video
Updated: Jun 2, 2026
Malachite Green Assay for the Discovery of Heat-Shock Protein 90 Inhibitors
Published on: January 20, 2023
Initial testing (Stage 1) of AT13387, an HSP90 inhibitor, by the pediatric preclinical testing program
Min H Kang1, C Patrick Reynolds, Peter J Houghton
1Texas Tech University Health Sciences Center, Lubbock, Texas 79430-6450, USA. min.kang@ttuhsc.edu
Insights
AT13387, a heat-shock protein 90 (HSP90) inhibitor, demonstrated cytotoxic effects in vitro. In vivo studies showed modest activity against solid tumors but no efficacy in leukemia models, indicating limited single-agent potential.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Heat-shock protein 90 (HSP90) is a crucial molecular chaperone involved in cancer cell survival.
- Inhibiting HSP90 is a therapeutic strategy explored for various cancers.
- AT13387 is a non-geldanamycin inhibitor targeting HSP90.
Purpose of the Study:
- To evaluate the in vitro and in vivo efficacy of AT13387.
- To assess the anti-cancer activity of AT13387 in solid tumor and leukemia xenograft models.
- To determine the single-agent activity of AT13387.
Main Methods:
- In vitro testing of AT13387 against the PPTP panel (1.0 nM to 10 µM).
- In vivo testing of AT13387 in PPTP xenograft models (40 or 60 mg/kg, oral administration twice weekly).
- Evaluation of efficacy based on median EC(50) values, cytotoxic effects, EFS distribution, and objective tumor responses.
Main Results:
- AT13387 exhibited a median EC(50) of 41 nM in vitro, consistent with cytotoxic activity.
- In vivo, AT13387 showed significant differences in EFS distribution in 17% of evaluable solid tumor xenografts.
- No objective tumor responses or significant activity was observed in ALL xenografts; overall single-agent activity was modest.
Conclusions:
- AT13387 displays in vitro cytotoxic effects against cancer cell lines.
- The compound demonstrates limited in vivo efficacy as a single agent, particularly in leukemia models.
- Further investigation may be needed to explore combination therapies or alternative applications for AT13387.
Abstract:
AT13387, a non-geldanamycin inhibitor of heat-shock protein 90 (HSP90), was tested against the PPTP in vitro panel (1.0 nM to 10 µM) and against the PPTP in vivo panels (40 or 60 mg/kg) administered orally twice weekly. In vitro AT13387 showed a median EC(50) value of 41 nM and exhibited activity consistent with a cytotoxic effect. In vivo AT13387 induced significant differences in EFS distribution compared to controls in 17% evaluable solid tumor xenografts, but in none of the ALL xenografts. No objective tumor responses were observed. In vivo AT13387 demonstrated only modest single agent activity.
