Stabilizers of the Max homodimer identified in virtual ligand screening inhibit Myc function.

ABSTRACT: Many human cancers show constitutive or amplified expression of the transcriptional regulator and oncoprotein Myc, making Myc a potential target for therapeutic intervention. Here we report the down-regulation of Myc activity by reducing the availability of Max, the essential dimerization partner of Myc. Max is expressed constitutively and can form unstable homodimers. We have isolated stabilizers of the Max homodimer by applying virtual ligand screening (VLS) to identify specific binding pockets for small molecule interactors. Candidate compounds found by VLS were screened by fluorescence resonance energy transfer, and from these screens emerged a potent, specific stabilizer of the Max homodimer. In vitro binding assays demonstrated that the stabilizer enhances the formation of the Max-Ma

SUBMITTER: Jiang H 

PROVIDER: S-EPMC2730382 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature