Discovery of a class of potent and selective non‐competitive sentrin‐specific protease 1 inhibitors

Lindenmann, Urs; Brand, Michael; Gall, Flavio; Frasson, David; Hunziker, Lukas; Kroslakova, Ivana; Sievers, Martin; Riedl, Rainer

doi:10.1002/cmdc.202000067

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 1860-7187
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.
URI:	https://digitalcollection.zhaw.ch/handle/11475/21813
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

Files in This Item:

There are no files associated with this item.

Show full item record

Lindenmann, U., Brand, M., Gall, F., Frasson, D., Hunziker, L., Kroslakova, I., Sievers, M., & Riedl, R. (2020). Discovery of a class of potent and selective non‐competitive sentrin‐specific protease 1 inhibitors. ChemMedChem, 15(8), 675–679. https://doi.org/10.1002/cmdc.202000067

Lindenmann, U. et al. (2020) ‘Discovery of a class of potent and selective non‐competitive sentrin‐specific protease 1 inhibitors’, ChemMedChem, 15(8), pp. 675–679. Available at: https://doi.org/10.1002/cmdc.202000067.

U. Lindenmann et al., “Discovery of a class of potent and selective non‐competitive sentrin‐specific protease 1 inhibitors,” ChemMedChem, vol. 15, no. 8, pp. 675–679, Feb. 2020, doi: 10.1002/cmdc.202000067.

LINDENMANN, Urs, Michael BRAND, Flavio GALL, David FRASSON, Lukas HUNZIKER, Ivana KROSLAKOVA, Martin SIEVERS und Rainer RIEDL, 2020. Discovery of a class of potent and selective non‐competitive sentrin‐specific protease 1 inhibitors. ChemMedChem. 21 Februar 2020. Bd. 15, Nr. 8, S. 675–679. DOI 10.1002/cmdc.202000067

Lindenmann, Urs, Michael Brand, Flavio Gall, David Frasson, Lukas Hunziker, Ivana Kroslakova, Martin Sievers, and Rainer Riedl. 2020. “Discovery of a Class of Potent and Selective Non‐Competitive Sentrin‐Specific Protease 1 Inhibitors.” ChemMedChem 15 (8): 675–79. https://doi.org/10.1002/cmdc.202000067.

Lindenmann, Urs, et al. “Discovery of a Class of Potent and Selective Non‐Competitive Sentrin‐Specific Protease 1 Inhibitors.” ChemMedChem, vol. 15, no. 8, Feb. 2020, pp. 675–79, https://doi.org/10.1002/cmdc.202000067.