KH-39

KH-39 is a potent, selective, small-molecule inhibitor of the RNA-binding protein Hu antigen R (HuR, encoded by ELAVL1), developed by researchers at the University of Kansas. HuR is frequently overexpressed in various cancers and inflammatory diseases, where it binds to AU-rich elements (AREs) in the 3'-untranslated regions (3'-UTRs) of oncogenic and pro-inflammatory mRNAs, enhancing their stability and translation. KH-39 binds to the RNA-binding pocket of HuR, effectively disrupting HuR-ARE interactions. In oncology, KH-39 has been shown to inhibit the HuR/CD147/IL-6 axis, reducing tumor cell proliferation, clonogenicity, and immune evasion, and synergizing with anti-PD-1 immunotherapy in preclinical models of breast and prostate cancers. Additionally, KH-39 has demonstrated therapeutic potential in preclinical models of septic acute kidney injury (AKI) transitioning to chronic kidney disease (CKD) by suppressing HuR-mediated renal inflammation and fibrosis, as well as in mitigating drug-induced hepatotoxicity.