Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1366058 | Bioorganic & Medicinal Chemistry Letters | 2007 | 6 Pages |
Abstract
Substituted pyrazole esters were identified as hits in a high throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR) to identify inhibitors of the enzyme cathepsin B. Members of this class, along with functional group analogs, were synthesized in an effort to define the structural requirements for activity. Analog characterization was hampered by the need to include a reducing agent such as dithiothreitol (DTT) or cysteine in the assay, highlighting the caution required in interpreting biological data gathered in the presence of such nucleophiles. Despite the confounding effects of DTT and cysteine, our studies demonstrate that the pyrazole 1 acts as alternative substrate for cathepsin B, rather than as an inhibitor.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Michael C. Myers, Andrew D. Napper, Nuzhat Motlekar, Parag P. Shah, Chun-Hao Chiu, Mary Pat Beavers, Scott L. Diamond, Donna M. Huryn, Amos B. III,