Structural highlights
Function
[CMA1_HUMAN] Major secreted protease of mast cells with suspected roles in vasoactive peptide generation, extracellular matrix degradation, and regulation of gland secretion.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
A series of beta-carboxamido-phosphon(in)ic acids (2) was identified as a new structural motif for obtaining potent inhibitors of human mast cell chymase. For example, 1-naphthyl derivative 5f had an IC50 value of 29 nM and (E)-styryl derivative 6g had an IC50 value of 3.5 nM. An X-ray structure for 5f.chymase revealed key interactions within the enzyme active site. Compound 5f was selective for inhibiting chymase versus eight serine proteases. Compound 6h was orally bioavailable in rats (F=39%), and orally efficacious in a hamster model of inflammation.
Discovery of potent, selective, orally active, nonpeptide inhibitors of human mast cell chymase.,Greco MN, Hawkins MJ, Powell ET, Almond HR Jr, de Garavilla L, Hall J, Minor LK, Wang Y, Corcoran TW, Di Cera E, Cantwell AM, Savvides SN, Damiano BP, Maryanoff BE J Med Chem. 2007 Apr 19;50(8):1727-30. Epub 2007 Mar 16. PMID:17361995[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Greco MN, Hawkins MJ, Powell ET, Almond HR Jr, de Garavilla L, Hall J, Minor LK, Wang Y, Corcoran TW, Di Cera E, Cantwell AM, Savvides SN, Damiano BP, Maryanoff BE. Discovery of potent, selective, orally active, nonpeptide inhibitors of human mast cell chymase. J Med Chem. 2007 Apr 19;50(8):1727-30. Epub 2007 Mar 16. PMID:17361995 doi:10.1021/jm0700619
