biostudies-literatureBenbrook DMNEI NIH HHS412-23https://www.ebi.ac.uk/biostudies/studies/S-EPMC4045313biostudies-literatureUnknown32(3)SHetA2 is a small molecule flexible heteroarotinoid (Flex-Het) with promising cancer prevention and therapeutic activity. Extensive preclinical testing documented lack of SHetA2 toxicity at doses 25 to 150 fold above effective doses. Knowledge of the SHetA2 molecular target(s) that mediate(s) the mechanism of SHetA2 action is critical to appropriate design of clinical trials and improved analogs. The aim of this study was to develop a method to identify SHetA2 binding proteins in cancer cells. A known metabolite of SHetA2 that has a hydroxyl group available for attachment was synthesized and conjugated to a linker for attachment to a magnetic microsphere. SHetA2-conjugated magnetic microspheres and unconjugated magnetic microspheres were separately incubated with aliquots of a whole cell pInvestigational new drugsSHetA2 interference with mortalin binding to p66shc and p53 identified using drug-conjugated magnetic microspheres.PMC4045313EY017888R21 EY017888Berlin KDBenbrook DMNammalwar BMatsumoto HSingh ALong ABunce RAfalseSHetA2 interference with mortalin binding to p66shc and p53 identified using drug-conjugated magnetic microspheres.SHetA2 is a small molecule flexible heteroarotinoid (Flex-Het) with promising cancer prevention and therapeutic activity. Extensive preclinical testing documented lack of SHetA2 toxicity at doses 25 to 150 fold above effective doses. Knowledge of the SHetA2 molecular target(s) that mediate(s) the mechanism of SHetA2 action is critical to appropriate design of clinical trials and improved analogs. The aim of this study was to develop a method to identify SHetA2 binding proteins in cancer cells. A known metabolite of SHetA2 that has a hydroxyl group available for attachment was synthesized and conjugated to a linker for attachment to a magnetic microsphere. SHetA2-conjugated magnetic microspheres and unconjugated magnetic microspheres were separately incubated with aliquots of a whole cell p2014-01-01T00:00:00Z2014 Jun2026-04-07T16:13:31.965Z2025-05-31T23:45:22.668ZS-EPMC40453132425439010.1007/s10637-013-0041-x