FHD-609

FHD-609 is a potent, selective, heterobifunctional protein degrader targeting bromodomain-containing protein 9 (BRD9), a component of the non-canonical BAF (ncBAF) chromatin remodeling complex. It is designed as a proteolysis-targeting chimera (PROTAC), consisting of an E3 ligase-binding moiety and a BRD9-binding moiety, which together induce ubiquitination and subsequent degradation of BRD9. The drug has demonstrated dose-dependent pharmacokinetics and pharmacodynamics in clinical studies, with evidence of extensive BRD9 degradation in tumor tissue leading to downregulation of cancer cell proliferation gene sets. Developed for intravenous administration, its primary indication has been advanced synovial sarcoma and SMARCB1-deficient tumors. Clinical development was paused following cardiac safety concerns (QTc prolongation). The developer is Foghorn Therapeutics[1][3][4][5][6].