Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: Discovery of a class of potent and selective non‐competitive sentrin‐specific protease 1 inhibitors
Authors: Lindenmann, Urs
Brand, Michael
Gall, Flavio
Frasson, David
Hunziker, Lukas
Kroslakova, Ivana
Sievers, Martin
Riedl, Rainer
et. al: No
DOI: 10.1002/cmdc.202000067
Published in: ChemMedChem
Volume(Issue): 15
Issue: 8
Page(s): 675
Pages to: 679
Issue Date: 21-Feb-2020
Publisher / Ed. Institution: Wiley
ISSN: 1860-7179
Language: English
Subjects: Drug design; Drug discovery; Inhibitors; Medicinal chemistry; Structure-activity relationship
Subject (DDC): 615: Pharmacology and therapeutics
Abstract: Sentrin-specific proteases (SENPs) are responsible for the maturation of small ubiquitin-like modifiers (SUMOs) and the deconjugation of SUMOs from their substrate proteins. Studies on prostate cancer revealed an overexpression of SENP1, which promotes prostate cancer progression as well as metastasis. Therefore, SENP1 has been identified as a novel drug target against prostate cancer. Herein, we report the discovery and biological evaluation of potent and selective SENP1 inhibitors. A structure-activity relationship (SAR) of the newly identified pyridone scaffold revealed allosteric inhibitors with very attractive in vitro ADMET properties regarding plasma binding and plasma stability for this challenging target. This study also emphasizes the importance of biochemical mode of inhibition studies for de novo designed inhibitors.
Fulltext version: Published version
License (according to publishing contract): Licence according to publishing contract
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:Publikationen Life Sciences und Facility Management

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