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Structurally-enabled progression of novel fragment hits for the epigenetic target BRD3

Fragment-based drug discovery (FBDD) is a successful approach to hit finding in modern drug discovery and is proving particularly valuable for bromodomain-containing proteins, an emerging family of epigenetic regulators with potential as drug targets. We applied our integrated FBDD platform to the discovery of compounds targeting bromodomain-containing protein 3 (BRD3). Belonging to the bromodomain and extra-terminal motif (BET) family, BRD3 functions by binding acetylated lysine residues on chromatin and transcriptional regulators and is implicated in several disease phenotypes, including prostate cancer, medulloblastoma and NUT midline carcinoma.

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