Reactivation of p53: from peptides to small molecules.

摘要: Approximately 27 million people are living with a tumour in which the suppressing activity of p53 has been inactivated. In half these tumours, itself is not mutated but pathway partially abrogated. Mechanisms include overexpression negative regulators p53, such as MDM2 and MDM4, deletion or epigenetic inactivation positive ARF. other inactivated, ∼95% mutations lie core DNA-binding domain, reflects key role transcriptional activator. Reactivation suppressive properties therapeutic goal, use peptides research led directly to development two alternative small molecule approaches: stabilization mutant rescue its inhibition MDM4.