Title: Targeted polypharmacology : discovery of a highly potent non-hydroxamate dual matrix metalloproteinase (MMP)-10/-13 inhibitor
Authors : Senn, Nicole
Ott, Michael
Lanz, Jan
Riedl, Rainer
Published in : Journal of Medicinal Chemistry
Volume(Issue) : 60
Issue : 23
Pages : 9585
Pages to: 9598
Publisher / Ed. Institution : American Chemical Society
Issue Date: 2017
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (Publication)
Language : English
Subjects : Drug design; Humans; Matrix metalloproteinase 10; Matrix metalloproteinase 13; Matrix metalloproteinase inhibitors; Molecular models; Polypharmacology; Structure-activity relationship
Subject (DDC) : 572: Biochemistry
615: Pharmacology and therapeutics
Abstract: Matrix metalloproteinases (MMPs) play a key role in many diseases like cancer, atherosclerosis or arthritis. Interest in MMP inhibition has been revitalized very recently as the knowledge on the underlying network of biological pathways is steadily growing. On the basis of this new insight into the relevance of MMP-10 and MMP-13 within the MMP network and the ban of hydroxamate inhibitors from clinical development, the discovery of non-hydroxamate multitarget drugs against specific MMPs is of foremost interest. Here, we disclose the discovery of a very potent and selective non-hydroxamate MMP-10/-13 inhibitor. The high potency (IC50of 31 nM [MMP-10] and 5 nM [MMP-13]) and selectivity over MMP-1, -2, -3, -7, -8, -9, -12, and -14 enable this compound to decipher disease causing MMP networks and to generate new treatment options through targeted polypharmacology.
Departement: Life Sciences und Facility Management
Publication type: Article in scientific Journal
DOI : 10.1021/acs.jmedchem.7b01001
ISSN: 0022-2623
URI: https://digitalcollection.zhaw.ch/handle/11475/2915
Appears in Collections:Publikationen Life Sciences und Facility Management

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