NNU546

NNU546 is an orally available small molecule prodrug of the dipeptidyl boronic acid NNU219, developed by Jiangsu Chia Tai Fenghai Pharmaceutical Co. Ltd. in collaboration with China Pharmaceutical University and Nanjing Normal University. It is primarily investigated for the treatment of multiple myeloma. Upon oral administration, NNU546 is rapidly hydrolyzed to its active form, NNU219, which selectively and irreversibly inhibits the chymotrypsin-like (CT-L) activity of the 20S proteasome. This inhibition leads to the accumulation of ubiquitinated proteins, triggering an endoplasmic reticulum (ER) stress response, downregulation of the NF-κB signaling pathway, and induction of G2/M-phase cell cycle arrest and apoptosis in cancer cells. Preclinical studies suggest NNU546 possesses superior in vivo antitumor efficacy and more sustained pharmacodynamic inhibition compared to first-generation proteasome inhibitors like bortezomib.

Other names

Compound 6aCompound6aCompound-6a