Journal ArticleDOI
Michael Acceptors as Cysteine Protease Inhibitors
Maria M. M. Santos,Rui Moreira +1 more
TLDR
This review emphasizes on the new developments from literature reports on Michael acceptors as potential cysteine protease inhibitors, namely vinyl sulfones, alpha,beta-unsaturated carbonyl derivatives and aza-peptides.Abstract:
Cysteine proteases selectively catalyze the hydrolysis of peptide bonds. Uncontrolled, unregulated, or undesired proteolysis can lead to many disease states including emphysema, stroke, viral infections, cancer, Alzheimer's disease, inflammation, and arthritis. Cysteine proteases inhibitors thus have considerable potential utility for therapeutic intervention in a variety of disease states. This review emphasizes on the new developments from literature reports on Michael acceptors as potential cysteine protease inhibitors, namely vinyl sulfones, alpha,beta-unsaturated carbonyl derivatives and aza-peptides. These compounds irreversibly alkylate the active site cysteine residue via conjugate addition. Examples of Michael acceptors inhibitors that have already progressed to clinical testing are also presented.read more
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Journal ArticleDOI
Organic carbamates in drug design and medicinal chemistry.
TL;DR: In this article, the authors present properties and stabilities of carbamates, reagents and chemical methodologies for the synthesis of caramates and their applications in drug design and medicinal chemistry.
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Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles
Iana M. Serafimova,Miles A. Pufall,Miles A. Pufall,Shyam Krishnan,Katarzyna Duda,Michael S. Cohen,Michael S. Cohen,Rebecca L. Maglathlin,Jesse M. McFarland,Rand M. Miller,Morten Frödin,Jack Taunton,Jack Taunton +12 more
TL;DR: It is shown that electron-deficient olefins, including acrylamides, can be tuned to react with cysteine thiols in a rapidly reversible manner and establishes a chemistry-based framework for engineering sustained covalent inhibition without accumulating permanently modified proteins and peptides.
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Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity.
Hongbin He,Hua Jiang,Yun Chen,Jin Ye,Aoli Wang,Chao Wang,Qingsong Liu,Gaolin Liang,Xianming Deng,Wei Jiang,Rongbin Zhou +10 more
TL;DR: Ori can be covalently linked to NLRP3 to prevent assembly of theNLRP3 inflammasome, and to ameliorate inflammation in several mouse disease models, and could serve as a lead for developing new therapeutics against NL RP3-driven diseases.
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Boron containing compounds as protease inhibitors.
Journal ArticleDOI
Recent insights into the molecular mechanisms of the NLRP3 inflammasome activation.
TL;DR: The current knowledge on the molecular events that lead to activation of the NLRP3 inflammasome in response to a range of K + efflux-inducing danger signals is summarized and the reported involvement of cytosolic Ca 2+ fluxes onNLRP3 activation is commented on.