Disruption of the Interaction of the Androgen Receptor with Chromatin: A Novel Therapeutic Approach in Prostate Cancer
Technical Report,08 Sep 2015,07 Sep 2016
University of Texas Southwestern Medical Center Dallas United States
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We have made significant progress in our work with small molecules including peptidespeptidomimetics to disrupt the interaction between androgen receptor and critical coregulators, such as the pioneering transcription factor FOXA1 on the DNA. We have shown that the interface between AR-FOXA1 plays important roles in AR responsiveness and activity. We have designed, synthesized, and tested a panel of peptidespeptidomimetics to disrupt the interaction between AR andFOXA1. The effects of these candidate compounds have been tested in multiple assays and various prostate cancer cell lines. We have further utilized and refined the potent and sensitive NanoBit in vivo complementation assay to evaluate other possible reagents through high throughput screening strategy. We are now in the process of comparing and confirming these lead compounds in prostate cancer models. In the coming year, we intend to further optimize these compounds and complete the proposed mechanistic studies.
- Medicine and Medical Research