QDD-7

QDD-7 is a novel small molecule inhibitor of the E3 ubiquitin ligase HUWE1. Developed by researchers at Queen's University Belfast, QDD-7 targets HUWE1 to disrupt its role in promoting the formation of c-MYC multimers surrounding stalled replication forks, which normally protects cancer cells against DNA damage. In preclinical models of multiple myeloma, treatment with QDD-7 effectively inhibits HUWE1 activity, leading to reduced c-MYC protein expression, induction of DNA damage (as indicated by γH2AX), and apoptosis. When combined with the proteasome inhibitor bortezomib, QDD-7 demonstrates synergistic anti-myeloma activity, particularly when administered sequentially with bortezomib pre-treatment.