Discovery and characterization of small molecules targeting the DNA-binding ETS domain of ERG in prostate cancer.

ABSTRACT: Genomic alterations involving translocations of the ETS-related gene ERG occur in approximately half of prostate cancer cases. These alterations result in aberrant, androgen-regulated production of ERG protein variants that directly contribute to disease development and progression. This study describes the discovery and characterization of a new class of small molecule ERG antagonists identified through rational in silico methods. These antagonists are designed to sterically block DNA binding by the ETS domain of ERG and thereby disrupt transcriptional activity. We confirmed the direct binding of a lead compound, VPC-18005, with the ERG-ETS domain using biophysical approaches. We then demonstrated VPC-18005 reduced migration and invasion rates of ERG expressing prostate cancer cells, and

SUBMITTER: Butler MS 

PROVIDER: S-EPMC5522078 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature