Current Topics in Medicinal Chemistry

Allen B. Reitz
Fox Chase Chemical Diversity Center, Inc.
Doylestown, PA
USA

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The Identification, Characterization and Optimization of Small Molecule Probes of Cysteine Proteases: Experiences of the Penn Center for Molecular Discovery with Cathepsin B and Cathepsin L

Author(s): Donna M. Huryn and Amos B. Smith III

Affiliation: Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104- 6323, USA.

Abstract:

During the pilot phase of the NIH Molecular Library Screening Network, the Penn Center for Molecular Discovery focused on a series of projects aimed at high throughput screening and the development of probes of a variety of protease targets. This review provides our medicinal chemistry experience with two such targets - cathepsin B and cathepsin L. We describe our approach for hit validation, characterization and triage that led to a critical understanding of the nature of hits from the cathepsin B project. In addition, we detail our experience at hit identification and optimization that led to the development of a novel thiocarbazate probe of cathepsin L.

Keywords: Cathepsin B, Cathepsin L, cysteine proteases, DTT, false positives, hit validation, hit triage, redox cycling, thiocarbazates

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Article Details

VOLUME: 9
ISSUE: 13
Page: [1206 - 1216]
Pages: 11
DOI: 10.2174/156802609789753653
Price: $58