1hy7

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spinqualitylabelsall models PDB ID 1hy7 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
, resolution 1.5Å
Ligands:	, and
Gene:	MMP3 (Homo sapiens)
Activity:	Stromelysin 1, with EC number 3.4.24.17
Coordinates:	save as pdb, mmCIF, xml

A CARBOXYLIC ACID BASED INHIBITOR IN COMPLEX WITH MMP3

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

A series of carboxylic acids were prepared from a propargylglycine scaffold and tested for efficacy as matrix metalloproteinase (MMP) inhibitors. Detailed SAR for the series is reported for four enzymes within the MMP family. The inhibitors were typically potent against collagenase-3 (MMP-13) and gelatinase A (MMP-2), while they spared collagenase-1 (MMP-1) and only moderately inhibited stromelysin (MMP-3). Compound 40 represents a typical inhibition profile of a compound with reasonable potency. Introduction of polar groups was required in order to generate inhibitors with acceptable water solubility, and this often resulted in a loss of potency as in compound 63. High serum protein binding proved to be a difficult hurdle with many compounds such as 48 showing >99% binding. Some compounds such as 64 displayed approximately 90% binding, but no reliable method was discovered for designing molecules with low protein binding. Finally, selected data regarding the pharmacokinetic behavior of these compounds is presented.

Disease

Known diseases associated with this structure: Coronary heart disease, susceptibility to OMIM:[185250]

About this Structure

1HY7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Development of new carboxylic acid-based MMP inhibitors derived from functionalized propargylglycines., Natchus MG, Bookland RG, Laufersweiler MJ, Pikul S, Almstead NG, De B, Janusz MJ, Hsieh LC, Gu F, Pokross ME, Patel VS, Garver SM, Peng SX, Branch TM, King SL, Baker TR, Foltz DJ, Mieling GE, J Med Chem. 2001 Mar 29;44(7):1060-71. PMID:11297453

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