TWQ-184

TWQ-184 is an experimental bifunctional small molecule and a member of a novel therapeutic class termed DNA Damage-Chemical Inducers of Proximity (DD-CIPs). Developed by researchers at institutions including Stanford University and Dana-Farber Cancer Institute, TWQ-184 is specifically designed to treat NUT carcinoma (NC), an aggressive squamous cancer driven by the BRD4-NUT fusion oncoprotein. The molecule functions by inducing the formation of a ternary complex between the BRD4-NUT fusion protein and Poly (ADP-ribose) polymerase (PARP). This proximity hijacks the oncogenic transcriptional activity of BRD4-NUT to recruit PARP to specific genomic loci, converting PARP-bound single-strand DNA breaks into lethal double-strand breaks. Preclinical studies demonstrate that TWQ-184 induces rapid γH2AX deposition and ATM activation, leading to potent and selective apoptosis in NC cell lines at nanomolar concentrations while maintaining a significant therapeutic window relative to healthy cells.