Geldanamycin and its derivatives as Hsp90 inhibitors

Fabio Bucchieri, Giuseppe Cicero, Alicja Kuban-Jankowska, Urszula Popowska, Alicja Sielicka-Dudzin, Magdalena Gorska, Wojciech Sawczuk, Magdalena Gorska, Narcyz Knap, Michal Wozniak

Research output: Contribution to journalArticlepeer-review

43 Citations (Scopus)

Abstract

The Hsp90 molecule, one of the most abundant heat shock proteins in mammalian cells, maintains homeostasis and prevents stress-induced cellular damage. Hsp90 is expressed under normal conditions at a level of about 1-2 Percent of total proteins, while its expression increases 2-10 fold in cancer cells. The two main constitutively expressed isoforms of Hsp90 are known as Hsp90-alpha and Hsp90-beta, and their upregulation is associated with tumor progression, invasion and formation of metastases, as well as development of drug resistance. The Hsp90 is a key target for many newly established, potent anticancer agents containing Hsp90 N-terminal ATP binding inhibitors, such as geldanamycin, and its analogues 17AAG and 17DMAG. The therapeutic usage of geldanamycin has been limited due to its poor water solubility and severe hepatotoxicity. Therefore, its analogues, including 17AAG, 17DMAG, Tanespimycin and Retaspimycin hydrochloride, with improved pharmacokinetic profiles, have been developed.
Original languageEnglish
Pages (from-to)2269-2277
Number of pages9
JournalFrontiers in Bioscience
Volume17
Publication statusPublished - 2012

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology

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