BI8622

BI8622 is a potent and selective small molecule inhibitor of the HECT-domain E3 ubiquitin ligase **HUWE1** (also known as ARF-BP1 or MULE). Developed by Boehringer Ingelheim as a chemical probe, BI8622 targets the C-terminal HECT domain of HUWE1, thereby preventing the ubiquitination and subsequent degradation or modulation of its substrates, including MYC, MCL1, and RPA70. In preclinical models of multiple myeloma and colorectal cancer, BI8622 has demonstrated the ability to impair the replicative stress response, increase DNA damage, and act synergistically with proteasome inhibitors such as bortezomib. While it is a valuable tool for studying the role of HUWE1 in genome stability and oncogenesis, it is primarily utilized in research settings and has not yet advanced into clinical development.