Linked Life Data

12499575

Source:http://linkedlifedata.com/resource/pubmed/id/12499575

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-12-24
pubmed:abstractText
Chymase leading to tissue remodeling is expected to be a potent pharmaceutical target. Its functions in vivo are still unclear, because of lack of orally available inhibitors. Recently, however, the chymase inhibitor NK3201 (2-(5-formylamino-6-oxo-2-phenyl-1,6-dihydropyrimidin-1-yl)-N-[[3,4-dioxo-1-phenyl-7-(2-pyridyloxy)]-2-heptyl] acetamide) was demonstrated to have oral activity against neointimal hyperplasia in dog models (Takai S. et al., Life Sci 69, 1725 - 1732 (2001)). In this review, by showing the efficacy of NK3201 in some hamster models, chymase functions in vivo are summarized, and the potency of this chymase inhibitor is introduced. In vitro study, NK3201 showed potent chymase specific inhibitory activity, and Dixon plot analysis indicated competitive inhibition. Oral administration of NK3201 into normal rats resulted in rapid spread over every tissue except the brain, and sufficient activity to inhibit tissue chymase was detected even after 24 h. In passive cutaneous anaphylaxis, myocardial infarction and bleomycin-induced pulmonary fibrosis models, orally administered NK3201 showed potent inhibition of inflammatory response, tissue angiotensin II formation, and fibrosis, respectively. These data suggest that chymase has a vital role in tissue remodeling through promotion of the inflammatory response, tissue angiotensin II and tissue fibrosis. Our recent data indicated chymase participation in bladder fibrosis, like interstitial cystitis. Therefore, the orally active chymase inhibitor NK3201 may have protective effects on tissue remodeling in several diseases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-5198
pubmed:author
pubmed:issnType
Print
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
218-22
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Development of the chymase inhibitor as an anti-tissue-remodeling drug: myocardial infarction and some other possibilities.
pubmed:affiliation
Research & Development Division, Pharmaceuticals Group, Nippon Kayaku Co., Ltd., Tokyo, Japan. yoshikazu.sukenaga@nipponkayaku.co.jp
pubmed:publicationType
Journal Article, Review