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JMX1123 is a proteolysis-targeting chimera (PROTAC) protein degrader designed to target and degrade Signal Transducer and Activator of Transcription 3 (STAT3). Developed by researchers at the Louisiana State University Health Sciences Center and the University of Texas Medical Branch, JMX1123 is based on the lead STAT3 inhibitor HJC0152 (an O-alkylamino tethered derivative of niclosamide). JMX1123 functions by recruiting an E3 ubiquitin ligase to STAT3, leading to its ubiquitination and subsequent proteasomal degradation. In preclinical studies, JMX1123 has demonstrated potent antiproliferative and apoptotic activity against breast cancer cell lines, including triple-negative breast cancer (TNBC) and estrogen receptor (ER)-positive breast cancer, by significantly reducing total STAT3 protein levels and inhibiting STAT3 phosphorylation at Tyr705 and Ser727.
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