%0 Journal Article
%T Strategies for Discovery of Small Molecule Radiation Protectors and Radiation Mitigators
%A Joel S. Greenberger
%A Michael W. Epperly
%J Frontiers in Oncology
%D 2012
%I Frontiers Media
%R 10.3389/fonc.2011.00059
%X Mitochondrial targeted radiation damage protectors (delivered prior to irradiation) and mitigators (delivered after irradiation, but before the appearance of symptoms associated with radiation syndrome) have been a recent focus in drug discovery for (1) normal tissue radiation protection during fractionated radiotherapy, and (2) radiation terrorism counter measures. Several categories of such molecules have been discovered: nitroxide-linked hybrid molecules, including GS-nitroxide, GS-nitric oxide synthase inhibitors, p53/mdm2/mdm4 inhibitors, and pharmaceutical agents including inhibitors of the phosphoinositide-3-kinase pathway and the anti-seizure medicine, carbamazepine. Evaluation of potential new radiation dose modifying molecules to protect normal tissue includes: clonogenic radiation survival curves, assays for apoptosis and DNA repair, and irradiation-induced depletion of antioxidant stores. Studies of organ specific radioprotection and in total body irradiation-induced hematopoietic syndrome in the mouse model for protection/mitigation facilitate rational means by which to move candidate small molecule drugs along the drug discovery pipeline into clinical development.
%K radiation mitigators
%K radioprotectors
%K small molecules
%K mitochondria
%U http://www.frontiersin.org/Journal/10.3389/fonc.2011.00059/abstract