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The G-quadruplex (G4) is an alternate state of DNA, formed when guanines hydrogen bond to each other and stack to form a unique structure. G4s cluster in DNA regions controlling replication, translation, transcription, and repair. The G4s in the promoter regions of cancer genes MYC and KRAS are frequently dysregulated in ovarian cancer. MYC is a proto-oncogene that regulates cell proliferation, growth, differentiation, and apoptosis. KRAS is a proto-oncogene that regulates cell growth and apoptosis. The goal of this project was to test various compounds for their interaction with the G4 using the FRET Melt2 assay. Stabilization of the G4 indicates that a compound may decrease the expression of MYC or KRAS and limit cancer growth. The compounds identified as stabilizers of G4 were then tested for cytotoxicity in SKOV3 ovarian cancer cells. Of these compounds, KN242 was shown to increase the stabilization of the G-quadruplex and decrease cellular viability.



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Stabilization of the G-quadruplex in Oncogenes MYC and KRAS as a Potential Ovarian Cancer Treatment