H174

H174 is a preclinical-stage, small-molecule inhibitor of signal transducer and activator of transcription 3 (STAT3). Developed by researchers at the University of Hawaii and Cedars-Sinai Medical Center, and licensed to Novella, LLC, H174 belongs to a series of (R)-azetidine-2-carboxamide-based compounds designed to directly target STAT3. It selectively inhibits STAT3 DNA-binding activity with nanomolar potency (IC50 of 300–800 nM) and high affinity (KD of 3.7 nM), showing minimal activity against other STAT family members like STAT1 and STAT5. In preclinical studies, H174 has demonstrated the ability to block constitutive STAT3 phosphorylation (Tyr705) and DNA-binding activity, leading to the inhibition of cell growth, colony formation, and oncogenic transformation in triple-negative breast cancer (TNBC) cell lines.