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Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives were investigated as novel small molecule amplifiers of heat shock factor 1 transcriptional activity. Lead optimization led to the discovery of compound 4A-13, which displayed potent HSF1 activity under mild heat stress (EC 50 =2.5μM) and significant cytoprotection in both rotenone (EC 50 =0.23μM) and oxygen-glucose deprivation...
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