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

Title: 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

Volume: 9 Issue: 13

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

Affiliation:

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

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.

Cite this article as:

Huryn M. Donna and Smith III B. Amos, 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, Current Topics in Medicinal Chemistry 2009; 9 (13) . https://dx.doi.org/10.2174/156802609789753653