Smith, Amos B
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Publication Orientational Phase Transition in NaxC60 (1 < x < 3)(1993-08-30) Yildirim, Taner; Fischer, John E; Harris, A. Brooks; Stephens, Peter W; Smith, Amos B; Liu, Dan; Brard, Laurent; Strongin, Robert MX-ray diffraction and calorimetry data on cubic NaxC60(1Publication Identification of Novel Inhibitors of Dietary Lipid Absorption using Zebrafish(2010-08-25) Clifton, Justin D; Lucumi, Edinson; Smith, Amos B; Huryn, Donna M; Myers, Michael C; Diamond, Scott L; Napper, Andrew; Pack, Michael; Hama, Kotaro; Farber, Steven APharmacological inhibition of dietary lipid absorption induces favorable changes in serum lipoprotein levels in patients that are at risk for cardiovascular disease and is considered an adjuvant or alternative treatment with HMG-CoA reductase inhibitors (statins). Here we demonstrate the feasibility of identifying novel inhibitors of intestinal lipid absorption using the zebrafish system. A pilot screen of an unbiased chemical library identified novel compounds that inhibited processing of fluorescent lipid analogues in live zebrafish larvae. Secondary assays identified those compounds suitable for testing in mammals and provided insight into mechanism of action, which for several compounds could be distinguished from ezetimibe, a drug used to inhibit cholesterol absorption in humans that broadly inhibited lipid absorption in zebrafish larvae. These findings support the utility of zebrafish screening assays to identify novel compounds that target complex physiological processes.Publication Identification and synthesis of a unique thiocarbazate cathepsin L inhibitor(2008-01-01) Myers, Michael C; Diamond, Scott L; Shah, Parag P; Smith, Amos B; Huryn, Donna MLibrary samples containing 2,5-disubstituted oxadiazoles were identified as potent hits in a high throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR) directed at discovering inhibitors of cathepsin L. However, when synthesized in pure form, the putative actives were found to be devoid of biological activity. Analyses by LC–MS of original library samples indicated the presence of a number of impurities, in addition to the oxadiazoles. Synthesis and bioassay of the probable impurities led to the identification of a thiocarbazate that likely originated via ring opening of the oxadiazole. Previously unknown, thiocarbazates (-)-11 and (-)-12 were independently synthesized as single enantiomers and found to inhibit cathepsin 20 L in the low nanomolar range.