MS-444

MS-444 is a small molecule inhibitor of the RNA-binding protein HuR (ELAV-like protein 1), originally identified by Novartis. It acts by interfering with the homodimerization of HuR and inhibiting its nuclear-to-cytoplasmic translocation. By sequestering HuR in the nucleus, MS-444 prevents the protein from stabilizing AU-rich element (ARE)-containing mRNAs in the cytoplasm, such as those encoding the proto-oncogene PIM1, TNF-alpha, and COX-2. In preclinical models of pancreatic ductal adenocarcinoma (PDA), MS-444 has been shown to attenuate PIM1 expression and restore sensitivity to chemotherapeutic agents like oxaliplatin and 5-fluorouracil, suggesting its potential as a therapeutic strategy to overcome chemoresistance in aggressive malignancies.