Small Molecule AR-Ablative Agents
T2008-033 A new strategy for using androgen receptor ablative agents has been developed for prostate cancer therapy.
Hormone-refractory prostate cancer is incurable, and patients with this disease have few treatment options. Dysregulation of the androgen receptor (AR) is a hallmark of this incurable cancer. Molecular changes during cancer enhance AR sensitivity or permit AR activation by antiestrogen so that prostate cancer cells become resistant to androgen ablation therapy. Therefore, from a clinical perspective, targeting AR expression represents an important strategy to improve the treatment of androgen-independent prostate cancer.
Researchers at The Ohio State University, led by Dr. Ching-Shih Chen, discovered and developed AR-ablative agents with potent anti-tumor properties. Such compounds are expected to improve treatment of androgen-independent or hormone-refractory prostate cancer. The compounds were identified by recognizing that troglitazone and ciglitazone at high doses mediated PPAR-gamma independent transcriptional repression of AR in tumor cells. Optimization of troglitazone and ciglitazone gave rise to a novel class of AR-ablative agents with therapeutic potential for prostate cancer.
- Prostate cancer therapeutics
- Small molecular agents
- Overcomes androgen ablation resistance in prostate cancers
- Can treat HRPC, which is currently an incurable disease
- The IC 50 for lead compounds 12 and 16 has been found to be 2-4uM