Departmental Papers (CBE)

Document Type

Journal Article

Date of this Version

September 2007


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 alternate substrate for cathepsin B, rather than as an inhibitor.


Postprint version. Published in Bioorganic & Medicinal Chemistry Letters, Volume 17, Issue 17, September 2007, pages 4761-4766.
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cathepsin b, DTT, cysteine, alternate substrate, HTS, Q3 MLSMR, pyrazole esters



Date Posted: 26 October 2007

This document has been peer reviewed.