Up284

Up284 is a small molecule inhibitor of RPN13 (also known as ADRM1), a proteasome ubiquitin receptor located in the 19S regulatory particle of the 26S proteasome. Developed by 1Up Therapeutics, Up284 was designed as a drug-like successor to the prototype inhibitor RA190. The compound selectively binds to the Cys88 residue of RPN13, leading to the accumulation of polyubiquitinated proteins, induction of endoplasmic reticulum (ER) stress, and the generation of reactive oxygen species (ROS), which triggers apoptosis in solid tumors. Preclinical studies have demonstrated that Up284 is blood-brain barrier (BBB) penetrant and effective in models of glioblastoma, ovarian cancer, and breast cancer. It is suitable for both oral and intravenous administration.