Preclinical Testing the Therapeutic Potential of a Potent and Novel Small-Molecule Inhibitor of Bcl-2 as a Novel Therapy for Hormone-Refractory Prostate Cancer

Abstract

Targeting the anti-apoptotic Bcl-2 members using non-peptide small-molecule inhibitors is a new and exciting therapeutic strategy. Our work has led to the discovery of potent non-peptide small-molecule inhibitor apogossypolone that not only binds to Bcl-2 and Bcl-xL proteins but also McI-I. Consistent with its strong binding affinity to Bcl-2 members apogossypolone potently and effectively inhibits cancer cell growth in androgen-independent human prostate cancer PC-3 and DU-145 cell lines. Apogossypolone is well-tolerated in animals and has an excellent oral bioavailability. Extensive in vivo studies are being carried out to determine its antitumor activity in animal models of human prostate cancer. Apogossypolone may have a great therapeutic potential to be developed as an effective and non-toxic new therapy for the treatment of advanced androgen- independent human prostate cancer.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2006
Accession Number
ADA466688

Entities

People

  • Shaomeng Wang

Organizations

  • University of Michigan

Tags

DTIC Thesaurus Topics

  • Androgens
  • Apoptosis
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemotherapeutic Agents
  • Hormones
  • Inhibition
  • Inhibitors
  • Molecules
  • Neoplasms
  • Programmed Cell Death
  • Prostate
  • Prostate Cancer
  • Small Molecules

Fields of Study

  • Biology
  • Chemistry
  • Medicine

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Prostate Cancer Biology.
  • Toxicology/Environmental Toxicology