Linked Life Data

7916900

Source:http://linkedlifedata.com/resource/pubmed/id/7916900

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-11-7
pubmed:abstractText
We present a general drug discovery strategy to find novel inhibitors of tyrosine kinases. This scheme includes the production of initial protein targets for primary screening, an evaluation of enzyme potency and specificity, biochemical and biological effects on various cellular processes in whole-cell models, and strategies for in vivo evaluation of antitumor activity. These aspects are illustrated using a newly discovered class of tyrosine kinase inhibitors, the 2-thioindoles. Certain members of this class of compounds inhibit specific tyrosine kinases at low micromolar concentrations and exhibit a distinct structure-activity relationship, as well as enzyme specificity depending on the chemical substitution. These compounds suppress growth factor-mediated tyrosine phosphorylation and mitogenesis in viable cells and, in some cases, exhibit marked specificity for these effects depending on the substituents on the indole ring system. The issue is stressed that since inhibitors of signal transduction pathways represent an entirely new class of potential antitumor agents, distinct from past and currently used cancer therapies, alternative in vivo tumor models may be needed as well as different requirements for dose levels, scheduling and endpoint evaluation. These inherent difficulties emphasize a need for more basic research at the in vivo stage of drug evaluation to enhance model development and provide a better understanding of the pharmacology for these newer classes of drugs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0266-9536
pubmed:author
pubmed:issnType
Print
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
331-51
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Strategies for the discovery of novel tyrosine kinase inhibitors with anticancer activity.
pubmed:affiliation
Department of Cancer Research, Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, MI 48105.
pubmed:publicationType
Journal Article