CXB-7138

CXB-7138 is an orally bioavailable, first-in-class dual molecular glue degrader (MGD) developed by CoBX Bio. It utilizes a novel chemical scaffold to recruit the cereblon (CRBN) E3 ubiquitin ligase, inducing the selective proteasomal degradation of two distinct targets: GSPT1 (eRF3a), a translation termination GTPase, and ZFP91, an atypical E3 ligase and transcriptional regulator. Both GSPT1 and ZFP91 are frequently overexpressed in pancreatic ductal adenocarcinoma (PDAC) and correlate with poor prognosis. CXB-7138 has demonstrated potent sub-nanomolar to nanomolar antiproliferative activity across various cancer models, with enhanced sensitivity observed in SMAD4-altered PDAC cell lines. In preclinical studies, oral administration of CXB-7138 showed significant antitumor efficacy in PDAC xenograft models with a favorable safety profile.