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Novel small molecule mitigators of ionizing radiation

详细技术说明

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*Abstract

BackgroundCurrently there is a serious absence of pharmaceutically attractive small molecules that mitigate the lethal effects of an accidental or intentional public exposure to toxic doses of ionizing radiation. Moreover, cellular systems have not been established that emulate the radiobiologically relevant cell populations and that are suitable for high throughput screening.TechnologyInvestigators have developed and then used an unbiased phenotypic small interfering RNA (siRNA) assay to identify proteins with the potential of being drug targets for theprotection of human cell populations against clinically relevant ionizing radiation doses that cause acute radiation syndrome. A siRNA library comprising 5,520 genes known or hypothesized to be potential therapeutic targets was then screened and 29 siRNAs were identified as potential targets.One of the highest confidence candidate products was pi3kinase. When newly synthesized PI3K inhibitors were used, it was discovered that these inhibitors mitigatedradiation-induced apoptosis in human NCCIT.Application1. Treatment of acute radiation syndrome after the occurance of an unexpected release of radiation due to accident or natural disaster2. Treatment of radiation exposure due to a "dirty bomb"3. Treatment of the radiation side effects from cancer therapyAdvantages* Currently there are no drugs that can be administered to people who have been exposed to potentially harmful doses of radiationStage of Development* Animal data is availableProvisional Patent Application Filed

*Principal Investigation

Name: Michael Epperly, Associate Professor

Department: Med-Radiation Oncology

Name: Joel Greenberger, Professor & Chairman

Department: Med-Radiation Oncology

Name: John Lazo, Professor Emeritus

Department: Departments of Pharmacology & Chemistry

Name: Elizabeth Sharlow

Department: Med-Pharmacology and Chemical Biology

Name: Erin Skoda

Department: Chemistry

Name: Peter Wipf, Professor

Department: Chemistry

国家/地区

美国