Preclinical Testing the Therapeutic Potential of a Potent and Novel Small-molecule Inhibitor of Bc1-2 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 Mcl-1. 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. Our studies using the PC-3 androgen-independent xenograft model showed that Apogossypolone can enhance the antitumor activity of taxotere without causing any additional signs of toxicity, as compared to taxotere alone. Apogossypolone may have a promising therapeutic potential to be developed as an effective and non-toxic new therapy for the treatment of advanced, androgen-independent human prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2007
- Accession Number
- ADA483164
Entities
People
- Shaomeng Wang
Organizations
- University of Michigan