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First insight into structure-activity relationships of selective meprin β inhibitors.

Abstract：

:The astacin proteases meprin α and β are emerging drug targets for treatment of disorders such as kidney failure, fibrosis or inflammatory bowel disease. However, there are only few inhibitors of both proteases reported to date. Starting from NNGH as lead structure, a detailed elaboration of the structure-activity relationship of meprin β inhibitors was performed, leading to compounds with activities in the lower nanomolar range. Considering the preference of meprin β for acidic residues in the P1' position, the compounds were optimized. Acidic modifications induced potent inhibition and >100-fold selectivity over other structurally related metalloproteases such as MMP-2 or ADAM10.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Ramsbeck D,Hamann A,Schlenzig D,Schilling S,Buchholz M

doi

10.1016/j.bmcl.2017.04.012

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

2428-2431

issue

11

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(17)30375-X

journal_volume

27

pub_type

杂志文章

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