Small-molecule inhibitors of the p53 suppressor HDM2: have protein-protein interactions come of age as drug targets?

摘要

HDM2 is a negative regulator of the tumour suppressor p53. Because HDM2 is overexpressed in many cancers that retain wild-type p53, and because the effectiveness of chemotherapies that induce p53 might be limited by HDM2, inhibitors of the HDM2-p53 interaction are being sought as tumour-selective drugs. A binding site within HDM2 has been defined and blocking this site with peptides has been shown to induce p53 transcriptional activity. A recent report demonstrates in vivo proof of principle using drug-like small molecules that target HDM2.