Wang, C.; Diez, J.; Park, H.; Spicer, T.P.; Scampavia, L.D.; Becker-Pauly, C.; Fields, G.B.; Minond, D.; Bannister, T.D. Discovery and Optimization of Selective Inhibitors of Meprin α (Part II). Pharmaceuticals2021, 14, 197.
Wang, C.; Diez, J.; Park, H.; Spicer, T.P.; Scampavia, L.D.; Becker-Pauly, C.; Fields, G.B.; Minond, D.; Bannister, T.D. Discovery and Optimization of Selective Inhibitors of Meprin α (Part II). Pharmaceuticals 2021, 14, 197.
Wang, C.; Diez, J.; Park, H.; Spicer, T.P.; Scampavia, L.D.; Becker-Pauly, C.; Fields, G.B.; Minond, D.; Bannister, T.D. Discovery and Optimization of Selective Inhibitors of Meprin α (Part II). Pharmaceuticals2021, 14, 197.
Wang, C.; Diez, J.; Park, H.; Spicer, T.P.; Scampavia, L.D.; Becker-Pauly, C.; Fields, G.B.; Minond, D.; Bannister, T.D. Discovery and Optimization of Selective Inhibitors of Meprin α (Part II). Pharmaceuticals 2021, 14, 197.
Abstract
Meprin α is a zinc metalloproteinase (metzincin) that has been implicated in multiple diseases, including fibrosis and cancers. It has proven difficult to find small molecules that are capable of selectively inhibiting meprin α, or its close relative meprin β, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin α-specific inhibition through an HTS effort (see part I, preceding paper). In part II we report the optimization of a potent and selective hydroxamic acid meprin α inhibitor probe which may help define the therapeutic potential for small molecule meprin α inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition.
Keywords
meprin α; meprin β; zinc metalloproteinase; medicinal chemistry; probe development
Subject
Medicine and Pharmacology, Immunology and Allergy
Copyright:
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