Skip to main content
  • AACR Journals
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Radiation Oncology
      • Novel Combinations
      • Reviews
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • AACR Journals
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Cancer Therapeutics
Molecular Cancer Therapeutics
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Radiation Oncology
      • Novel Combinations
      • Reviews
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Preclinical Development

Ganetespib, a Unique Triazolone-Containing Hsp90 Inhibitor, Exhibits Potent Antitumor Activity and a Superior Safety Profile for Cancer Therapy

Weiwen Ying, Zhenjian Du, Lijun Sun, Kevin P. Foley, David A. Proia, Ronald K. Blackman, Dan Zhou, Takayo Inoue, Noriaki Tatsuta, Jim Sang, Shuxia Ye, Jamie Acquaviva, Luisa Shin Ogawa, Yumiko Wada, James Barsoum and Keizo Koya
Weiwen Ying
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhenjian Du
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lijun Sun
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kevin P. Foley
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David A. Proia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ronald K. Blackman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dan Zhou
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takayo Inoue
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Noriaki Tatsuta
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jim Sang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shuxia Ye
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jamie Acquaviva
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Luisa Shin Ogawa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yumiko Wada
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James Barsoum
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Keizo Koya
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/1535-7163.MCT-11-0755 Published February 2012
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Targeted inhibition of the molecular chaperone Hsp90 results in the simultaneous blockade of multiple oncogenic signaling pathways and has, thus, emerged as an attractive strategy for the development of novel cancer therapeutics. Ganetespib (formerly known as STA-9090) is a unique resorcinolic triazolone inhibitor of Hsp90 that is currently in clinical trials for a number of human cancers. In the present study, we showed that ganetespib exhibits potent in vitro cytotoxicity in a range of solid and hematologic tumor cell lines, including those that express mutated kinases that confer resistance to small-molecule tyrosine kinase inhibitors. Ganetespib treatment rapidly induced the degradation of known Hsp90 client proteins, displayed superior potency to the ansamycin inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG), and exhibited sustained activity even with short exposure times. In vivo, ganetespib showed potent antitumor efficacy in solid and hematologic xenograft models of oncogene addiction, as evidenced by significant growth inhibition and/or regressions. Notably, evaluation of the microregional activity of ganetespib in tumor xenografts showed that ganetespib was efficiently distributed throughout tumor tissue, including hypoxic regions >150 μm from the microvasculature, to inhibit proliferation and induce apoptosis. Importantly, ganetespib showed no evidence of cardiac or liver toxicity. Taken together, this preclinical activity profile indicates that ganetespib may have broad application for a variety of human malignancies, and with select mechanistic and safety advantages over other first- and second-generation Hsp90 inhibitors. Mol Cancer Ther; 11(2); 475–84. ©2011 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

  • Received September 20, 2011.
  • Revision received November 22, 2011.
  • Accepted November 22, 2011.
  • ©2011 American Association for Cancer Research.
View Full Text
PreviousNext
Back to top
Molecular Cancer Therapeutics: 11 (2)
February 2012
Volume 11, Issue 2
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Cancer Therapeutics article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Ganetespib, a Unique Triazolone-Containing Hsp90 Inhibitor, Exhibits Potent Antitumor Activity and a Superior Safety Profile for Cancer Therapy
(Your Name) has forwarded a page to you from Molecular Cancer Therapeutics
(Your Name) thought you would be interested in this article in Molecular Cancer Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Ganetespib, a Unique Triazolone-Containing Hsp90 Inhibitor, Exhibits Potent Antitumor Activity and a Superior Safety Profile for Cancer Therapy
Weiwen Ying, Zhenjian Du, Lijun Sun, Kevin P. Foley, David A. Proia, Ronald K. Blackman, Dan Zhou, Takayo Inoue, Noriaki Tatsuta, Jim Sang, Shuxia Ye, Jamie Acquaviva, Luisa Shin Ogawa, Yumiko Wada, James Barsoum and Keizo Koya
Mol Cancer Ther February 1 2012 (11) (2) 475-484; DOI: 10.1158/1535-7163.MCT-11-0755

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Ganetespib, a Unique Triazolone-Containing Hsp90 Inhibitor, Exhibits Potent Antitumor Activity and a Superior Safety Profile for Cancer Therapy
Weiwen Ying, Zhenjian Du, Lijun Sun, Kevin P. Foley, David A. Proia, Ronald K. Blackman, Dan Zhou, Takayo Inoue, Noriaki Tatsuta, Jim Sang, Shuxia Ye, Jamie Acquaviva, Luisa Shin Ogawa, Yumiko Wada, James Barsoum and Keizo Koya
Mol Cancer Ther February 1 2012 (11) (2) 475-484; DOI: 10.1158/1535-7163.MCT-11-0755
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Disclosure of Potential Conflicts of Interest
    • Grant Support
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • BMS-754807 Enhances Gemcitabine Response in PDAC
  • PSMA-Specific BiTE Antibody
  • BiKEs and TriKEs Enhance NK Cell Effector Function
Show more Preclinical Development
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About MCT

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Molecular Cancer Therapeutics
eISSN: 1538-8514
ISSN: 1535-7163

Advertisement