Blocks 26S proteasome activity by inhibiting the ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14) activities of the 19S regulatory subunit without affecting the catalytic activity of the 20S core subunit. b-AP15 displays several differences to bortezomib including insensitivity to over-expression of the anti-apoptotic mediator Bcl-2 and anti-tumor activity in four solid tumor models.