Micah Gutman
Research Mentor: Xiafukaiti Xiakeer
Mentor Department: MCTP, Medicine
Author(s): Sharpkate Shaker, xiafukaiti xiakeer
Session: Session 2 (10:00 AM – 10:50 AM)
Presentation Type: Poster 119
Abstract
ERG is a transcription factor involved in prostate cancer (PCa), which is recorded to be one of the most fatal types of cancer in male patients. Current treatment methods utilize the hindering of androgen activity by androgen antagonists. However, in many instances the body is able to develop resistance to therapies that rely on androgen antagonists. ERG could be the perfect target when creating new therapies, as it is a protein involved in the proliferation of cancer cells. In prostate cancer, gene rearrangements are common, and have the ability to produce mutated proteins by accidental fusion of multiple DNA sequences. A mutated ERG protein is developed when genes TMPRSS2 and ERG fuse. Although targeting ERG is considered an excellent therapeutic, it is intrinsically disordered in many regions in addition to having low enzymatic activity, making it difficult to target. To target ERG, we conducted DSF screening targeting the ERG PNT domain. As a result, we found the lead small-molecule PBITE-1 which can selectively bind to the PNT domain of the ERG. We used biolayer interferometry (BLI) to test the binding affinity between PBITE-1 and the PNT domain. This finding establishes the ERG PNT domain as ligandable, and enables future development of the ERG directed binders.
