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• W169581638 abstract "Although some progress has been made in the treatment of cancer over the last sixty years, the majority of chemotherapeutics has fallen short. Because general chemotherapies that target DNA replication have only a limited efficacy and significant non-target side-effects, a new paradigm for cancer drug development has been adopted. Using a molecular targeted approach, new gene and protein targets have been identified and the development of chemotherapies that are specific to these targets has already begun. In this study, compounds that interact with two key cancer targets, the Gquadruplex of the c-Myc promoter and p-glycoprotein, have been investigated. By developing such compounds, improvements in treatment efficacy is anticipated with an aspiration for decreased mortality attributable to cancer. Formation of DNA secondary structures, such as the G-quadruplex, in the NHE III1 region of the c-Myc promoter has been shown to repress c-Myc transcription. Because c-Myc is an oncogene that is overexpressed in a variety of cancers, stabilization of the G-quadruplex by small molecules would be advantageous in cancer treatment. Using Fluorescence Resonance Energy Transfer, with Taq Polymerase Stop assays for confirmation, a group of compounds were identified that stabilize the c-Myc Gquadruplex structure. Using a colon cancer model, two compounds were shown to decrease c-Myc gene and protein expression. Also, exposure to the compounds for 48 hours results in an induction of caspase-3, indicative of apoptosis. Furthermore, surface plasmon resonance suggests that compound-induced stabilization of the c-Myc Gquadruplex can prevent sustained binding of the regulatory protein NM23-H2 by" @default.
• W169581638 created "2016-06-24" @default.
• W169581638 creator A5076081402 @default.
• W169581638 date "2008-01-01" @default.
• W169581638 modified "2023-09-27" @default.
• W169581638 title "Identification and development of novel compounds for the treatment of human cancers" @default.
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