Abstract
Screening of a metalloprotease library led to the identification of a thiol-based dual ACE/NEP inhibitor as a potent ACE2 inhibitor. Modifications of the P(1) benzyl moiety led to improvements in ACE2 potency as well as to increased selectivity versus ACE and NEP.
MeSH terms
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Angiotensin-Converting Enzyme 2
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Angiotensin-Converting Enzyme Inhibitors / chemistry*
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Angiotensin-Converting Enzyme Inhibitors / metabolism
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Angiotensin-Converting Enzyme Inhibitors / pharmacology
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Animals
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Female
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Male
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Mice
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Mice, Inbred C57BL
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Peptidyl-Dipeptidase A / drug effects*
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Peptidyl-Dipeptidase A / genetics
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Structure-Activity Relationship
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Substrate Specificity
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Sulfhydryl Compounds / chemistry*
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Sulfhydryl Compounds / metabolism
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Sulfhydryl Compounds / pharmacology
Substances
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Angiotensin-Converting Enzyme Inhibitors
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Sulfhydryl Compounds
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Peptidyl-Dipeptidase A
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Ace2 protein, mouse
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Angiotensin-Converting Enzyme 2