Invention:
c-Myc is an essential transcription factor that plays an important role in cell proliferation, differentiation, as well as maintenance of other cell-cycle functions. Under pathologic conditions, c-Myc expression is highly elevated, contributing to development of malignancy in majority of human cancers. Thus researchers have been looking for compounds that will attenuate cMyc expression as a novel therapy for cancer. The Hurley lab previously discovered that stabilization of a specific G-quadruplex structure formed in the c-MYC promoter region functions as a transcriptional repressor element. This invention identifies new chemical entities (NCEs) that, according to FRET assay, target the G-quadruplex secondary DNA structure. The disclosed NCEs possess structural features with side chains that may improve potency with specificity over previously reported c-Myc suppressors.
c-Myc has also been implicated in progression of arterial disease (proliferation of atherosclerotic plaques). Thus NCEs that target cMyc in tumor cells may also be useful in treatment of obstructive vascular disease.
