Linked Life Data

18582861

Source:http://linkedlifedata.com/resource/pubmed/id/18582861

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-3
pubmed:dateCreated
2008-8-4
pubmed:abstractText
ASP4,000, (2S)-1-{[(1R,3S,4S,6R)-6-hydroxy-2-azabicyclo[2.2.1]hept-3-yl]carbonyl}-2-pyrrolidinecar bonitrile hydrochloride, is a novel dipeptidyl peptidase (DPP) 4 inhibitor. In the present study, we characterized the compound as an oral antidiabetic agent both in vitro and in vivo. ASP4,000 inhibited human recombinant DPP4 with an IC(50) value of 2.25 nM, and the enzyme-kinetic curve indicated that the inhibition type was competitive. In addition, ASP4,000 also potently inhibited DPP4 activity in human, rat, dog, and monkey plasma at concentrations of the order of 10(-9) M, and showed high selectivity against other related enzymes, including DPP8 and DPP9. The antihyperglycemic activity of ASP4,000 in vivo was examined using Zucker fa/fa rats, a type 2 diabetes animal model. A single oral administration of ASP4,000 at doses of 0.03-1 mg/kg suppressed plasma DPP4 activity, and then reduced the glucose level with increasing the active GLP-1 and insulin levels in oral glucose tolerance test. These results indicate that ASP4,000 is a potent, competitive, selective DPP4 inhibitor with antihyperglycemic activity, and could be a promising candidate agent for the treatment of patients with type 2 diabetes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
590
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
444-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
ASP4,000, a novel, selective, dipeptidyl peptidase 4 inhibitor with antihyperglycemic activity.
pubmed:affiliation
Drug Discovery Research, Astellas Pharma Inc., Osaka and Tsukuba, Japan. keiko.tanaka@jp.astellas.com
pubmed:publicationType
Journal Article