Hdm-2 (human double minute-2; Mdm-2 in mouse) is a ubiquitin ligase and key negative regulator of p53, targeting it for proteasomal degradation. Overexpression of Hdm-2 in some tumors leads to inactivation of p53, thereby allowing tumor cells to escape p53-induced apoptosis. HLI 373 is an inhibitor of Hdm-2. At concentrations of 5-50 μM, it selectively inhibits autoubiquitylation of Hdm-2 as well as the ubiquitylation and degradation of p53. Through these actions, HLI 373 stabilizes p53 and increases p53-dependent transcription, inducing apoptosis of transformed cells, tumor cells, and mouse embryo fibroblasts harboring wild-type p53.
