AI Article Synopsis
- * A series of new α-amidobenzylboronates were tested and showed strong potential as covalent inhibitors of PKa, with significant time-dependent inhibition effects (IC 66 nM at 1 min and 70 pM at 24 h).
- * These new compounds were found to inhibit PKa in a way that seems irreversible, similar to a known covalent PKa inhibitor (PPACK), indicating a strong potential for therapeutic use.
Article Abstract
Hereditary angioedema (HAE), a rare genetic disorder, is associated with uncontrolled plasma kallikrein (PKa) enzyme activity leading to the generation of bradykinin swelling in subcutaneous and submucosal membranes in various locations of the body. Herein, we describe a series of potent α-amidobenzylboronates as potential covalent inhibitors of PKa. These compounds exhibited time-dependent inhibition of PKa (compound IC 66 nM at 1 min, 70 pM at 24 h). Further compound dissociation studies demonstrated that showed no apparent reversibility comparable to d-Phe-Pro-Arg-chloromethylketone (PPACK) (), a known nonselective covalent PKa inhibitor.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017388 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.3c00572 | DOI Listing |
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