2. Academic Validation
  3. Synthesis and biological evaluation of 9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile analogues as potential inhibitors of deubiquitinating enzymes

Synthesis and biological evaluation of 9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile analogues as potential inhibitors of deubiquitinating enzymes

  • ChemMedChem. 2010 Apr 6;5(4):552-8. doi: 10.1002/cmdc.200900409.
Matteo Colombo 1,  Stefania Vallese,  Ilaria Peretto,  Xavier Jacq,  Jean-Christophe Rain,  Frédéric Colland,  Philippe Guedat
Affiliations

Affiliation

  • 1 NiKem Research, via Zambeletti 25, 20021 Baranzate, Milan, Italy. matteo.colombo@nikemresearch.com
PMID: 20186914 DOI: 10.1002/cmdc.200900409
Abstract

High-throughput screening highlighted 9-oxo-9H-indeno[1,2-b]pyrazine-2,3-dicarbonitrile (1) as an active inhibitor of ubiquitin-specific proteases (USPs), a family of hydrolytic Enzymes involved in the removal of ubiquitin from protein substrates. The chemical behavior of compound 1 was examined. Moreover, the synthesis and in vitro evaluation of new compounds, analogues of 1, led to the identification of potent and selective inhibitors of the deubiquitinating Enzyme USP8.

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