Linked Life Data

16847144

Source:http://linkedlifedata.com/resource/pubmed/id/16847144

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2006-9-25
pubmed:abstractText
In vivo screening of compounds for potential pharmacological activity is more advantageous than in vitro screening. In vivo screens eliminate the isolation of compounds that cannot cross biological membranes, are cytotoxic, or are not specific to the target. However, animal-based or even cell-based systems are usually expensive, time-consuming, and laborious. Here we describe the identification of inhibitors of the mitogen-activated protein kinase p38alpha via a high throughput screen using yeast cells. p38alpha is hyperactive in inflammatory diseases, and various indications suggest that its inhibition would reverse inflammation. However, there are currently no p38alpha inhibitors in clinical use. Because the human p38alpha imposes severe growth retardation when expressed in yeast, we screened a library of 40,000 randomly selected small molecules for compounds that would restore a normal growth rate. We identified two compounds; both share a structural motif of 4-benzylpiperidine, and both were shown to be efficient and selective p38alpha inhibitors in vitro. They were also active in mammalian cells, as manifested by their ability to reversibly inhibit myoblast differentiation. Thus, the yeast screen identified efficient and specific p38alpha inhibitors that are capable of crossing biological membranes, are not toxic, and function in mammalian cells. The rapid and cost-efficient high-throughput screening used here could be applied for isolation of inhibitors of various targets.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1395-405
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16847144-Amino Acid Motifs, pubmed-meshheading:16847144-Animals, pubmed-meshheading:16847144-Cell Differentiation, pubmed-meshheading:16847144-Cell Line, pubmed-meshheading:16847144-Cell Proliferation, pubmed-meshheading:16847144-Drug Evaluation, Preclinical, pubmed-meshheading:16847144-Dual Specificity Phosphatase 1, pubmed-meshheading:16847144-Mitogen-Activated Protein Kinase 14, pubmed-meshheading:16847144-Molecular Structure, pubmed-meshheading:16847144-Myoblasts, pubmed-meshheading:16847144-Phenotype, pubmed-meshheading:16847144-Phosphorylation, pubmed-meshheading:16847144-Protein Phosphatase 1, pubmed-meshheading:16847144-Protein Tyrosine Phosphatases, pubmed-meshheading:16847144-Rats, pubmed-meshheading:16847144-Substrate Specificity, pubmed-meshheading:16847144-Time Factors, pubmed-meshheading:16847144-Yeasts
pubmed:year
2006
pubmed:articleTitle
JX401, A p38alpha inhibitor containing a 4-benzylpiperidine motif, identified via a novel screening system in yeast.
pubmed:affiliation
Jexys Pharmaceuticals Ltd., Jerusalem, Israel.
pubmed:publicationType
Journal Article, Evaluation Studies