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Discovery and Optimization of Selective Inhibitors of Meprin α (Part II).

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 a, or its close relative meprin b, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin a-specific inhibition through an HTS effort (see part I, preceding paper). Here, in part II, we report further efforts to optimize potency and selectivity. We hope that a hydroxamic acid meprin α inhibitor probe will help define the therapeutic potential for small molecule meprin a inhibition and spur further drug discovery efforts in the area of zinc metalloproteinase inhibition.

SUBMITTER: Wang C

PROVIDER: S-EPMC7997411 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Discovery and Optimization of Selective Inhibitors of Meprin α (Part II).

Wang Chao C Diez Juan J Park Hajeung H Spicer Timothy P TP Scampavia Louis D LD Becker-Pauly Christoph C Fields Gregg B GB Minond Dmitriy D Bannister Thomas D TD

Pharmaceuticals (Basel, Switzerland) 20210227 3

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 a, or its close relative meprin b, over numerous other metzincins which, if inhibited, would elicit unwanted effects. We recently identified possible molecular starting points for meprin a-specific inhibition through an HTS effort (see part I, preceding paper). Here, in par ...[more]

PMID: 33673639

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