Heat shock protein 90 (HSP90) is a molecular chaperone that plays a key role in protein folding and stabilization. Many HSP90 client proteins are overexpressed in cancer cells, and the cancer cells are dependent on HSP90 for growth and survival. Therefore, HSP90 has become a popular therapeutic target for many cancers.
In a recent study it was demonstrated that geldanamycin enhances retrograde transport of the bacterial protein toxin Shiga toxin to the Golgi apparatus in human epidermoid laryngeal carcinoma cells. This activity was shown to be partially mediated by activation of the p38-MK2 pathway, rather than a direct interaction with HSP90.
Although inhibition of HSP90 appears to be an effective target against cancer, geldanamycin is limited by its low aqueous solubility and high toxicity. Consequently, geldanamycin derivatives with improved pharmacological profiles have been developed. These include 17-Allylgeldanamycin and 17-Dimethylaminoethylamino demethoxygeldanamycin.
There are several interesting HSP90 inhibitors available through LKT Labs:
Dyve Lingelem AB, Hjelseth IA, et al. Geldanamycin enhances retrograde transport of Shiga toxin in HEp-2 cells. PLoS One. 2015 May 27;10(5):e0129214. PMID: 26017782.