Disruption of Myc-Max heterodimerization with improved cell-penetrating analogs of the small molecule 10074-G5.

ABSTRACT: The c-Myc (Myc) oncoprotein is a high-value therapeutic target given that it is deregulated in multiple types of cancer. However, potent small molecule inhibitors of Myc have been difficult to identify, particularly those whose mechanism relies on blocking the association between Myc and its obligate heterodimerization partner, Max. We have recently reported a structure-activity relationship study of one such small molecule, 10074-G5, and generated an analog, JY-3-094, with significantly improved ability to prevent or disrupt the association between recombinant Myc and Max proteins. However, JY-3094 penetrates cells poorly. Here, we show that esterification of a critical para-carboxylic acid function of JY-3-094 by various blocking groups significantly improves cellular uptake although it

SUBMITTER: Wang H 

PROVIDER: S-EPMC3757250 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature