bAP15

bAP15 is a small molecule inhibitor of the 19S regulatory particle-associated deubiquitylating enzymes (DUBs), specifically targeting **Ubiquitin carboxyl-terminal hydrolase L5 (UCHL5)** and **Ubiquitin-specific peptidase 14 (USP14)**. By inhibiting these enzymes, bAP15 blocks the degradation of polyubiquitinated proteins by the proteasome, leading to proteotoxic stress and apoptosis. It is primarily investigated as an anti-cancer agent, particularly in multiple myeloma and solid tumors like renal cell carcinoma (RCC). In RCC, it has shown potential to overcome resistance to mTOR inhibitors like temsirolimus by inducing cell cycle arrest and inhibiting proliferating cell nuclear antigen (PCNA). While bAP15 is widely used as a research tool, its derivative VLX1570 has been evaluated in clinical trials.