Targeted cancer therapy through 17-DMAG as an Hsp90 inhibitor: Overview and current state of the art.

Abstract

Heat shock protein 90 (Hsp90) is an evolutionary preserved molecular chaperone which mediates many cellular processes such as cell transformation, proliferation, and survival in normal and stress conditions. Hsp90 plays an important role in folding, maturation, stabilization and activation of Hsp90 client proteins which all contribute to the development, and proliferation of cancer as well as other inflammatory diseases. Functional inhibition of Hsp90 can have a massive effect on various oncogenic and inflammatory pathways, and will result in the degradation of their client proteins. This turns it into an interesting target in the treatment of different malignancies. 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) as a semi-synthetic derivative of geldanamycin, has several advantages over 17-Allylamino-17-demethoxygeldanamycin (17-AAG) such as higher water solubility, good bioavailability, reduced metabolism, and greater anti-tumour capability. 17-DMAG binds to the Hsp90, and inhibits its function which eventually results in the degradation of Hsp90 client proteins. Here, we reviewed the pre-clinical data and clinical trial data on 17-DMAG as a single agent, in combination with other agents and loaded on nanomaterials in various cancers and inflammatory diseases.

• Authors: Hassan Mellatyar, Sona Talaei, Younes Pilehvar-Soltanahmadi, Abolfazl Barzegar, Abolfazl Akbarzadeh, Arman Shahabi, Mazyar Barekati-Mowahed, Nosratollah Zarghami
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 102 Pg. 608-617 (Jun 2018) ISSN: 1950-6007 [Electronic] France
• PMID: 29602128 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Benzoquinones
• HSP90 Heat-Shock Proteins
• Lactams, Macrocyclic
• 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin

Topics

• Animals
• Benzoquinones (therapeutic use)
• Clinical Trials as Topic
• Drug Discovery
• HSP90 Heat-Shock Proteins (antagonists & inhibitors, metabolism)
• Humans
• Lactams, Macrocyclic (therapeutic use)
• Molecular Targeted Therapy
• Neoplasms (drug therapy)