Targeted polypharmacology : discovery of a highly potent non-hydroxamate dual matrix metalloproteinase (MMP)-10/-13 inhibitor

Senn, Nicole; Ott, Michael; Lanz, Jan; Riedl, Rainer

doi:10.1021/acs.jmedchem.7b01001

Publication type:	Article in scientific journal
Type of review:	Peer review (publication)
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
DOI:	10.1021/acs.jmedchem.7b01001
Published in:	Journal of Medicinal Chemistry
Volume(Issue):	60
Issue:	23
Page(s):	9585
Pages to:	9598
Issue Date:	2017
Publisher / Ed. Institution:	American Chemical Society
ISSN:	0022-2623
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.
URI:	https://digitalcollection.zhaw.ch/handle/11475/2915
Fulltext version:	Published version
License (according to publishing contract):	Licence according to publishing contract
Departement:	Life Sciences and Facility Management
Appears in collections:	Publikationen Life Sciences und Facility Management

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Senn, N., Ott, M., Lanz, J., & Riedl, R. (2017). Targeted polypharmacology : discovery of a highly potent non-hydroxamate dual matrix metalloproteinase (MMP)-10/-13 inhibitor. Journal of Medicinal Chemistry, 60(23), 9585–9598. https://doi.org/10.1021/acs.jmedchem.7b01001

Senn, N. et al. (2017) ‘Targeted polypharmacology : discovery of a highly potent non-hydroxamate dual matrix metalloproteinase (MMP)-10/-13 inhibitor’, Journal of Medicinal Chemistry, 60(23), pp. 9585–9598. Available at: https://doi.org/10.1021/acs.jmedchem.7b01001.

N. Senn, M. Ott, J. Lanz, and R. Riedl, “Targeted polypharmacology : discovery of a highly potent non-hydroxamate dual matrix metalloproteinase (MMP)-10/-13 inhibitor,” Journal of Medicinal Chemistry, vol. 60, no. 23, pp. 9585–9598, 2017, doi: 10.1021/acs.jmedchem.7b01001.

SENN, Nicole, Michael OTT, Jan LANZ und Rainer RIEDL, 2017. Targeted polypharmacology : discovery of a highly potent non-hydroxamate dual matrix metalloproteinase (MMP)-10/-13 inhibitor. Journal of Medicinal Chemistry. 2017. Bd. 60, Nr. 23, S. 9585–9598. DOI 10.1021/acs.jmedchem.7b01001

Senn, Nicole, Michael Ott, Jan Lanz, and Rainer Riedl. 2017. “Targeted Polypharmacology : Discovery of a Highly Potent Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-10/-13 Inhibitor.” Journal of Medicinal Chemistry 60 (23): 9585–98. https://doi.org/10.1021/acs.jmedchem.7b01001.

Senn, Nicole, et al. “Targeted Polypharmacology : Discovery of a Highly Potent Non-Hydroxamate Dual Matrix Metalloproteinase (MMP)-10/-13 Inhibitor.” Journal of Medicinal Chemistry, vol. 60, no. 23, 2017, pp. 9585–98, https://doi.org/10.1021/acs.jmedchem.7b01001.