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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2010-2-19
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pubmed:abstractText |
Chemokine-like factor 1 (CKLF1) is a novel functional cytokine that acts through its receptor CC chemokine receptor 4 (CCR4). Activation of CCR4 by CKLF1 plays an important role in diseases such as asthma and multiple sclerosis. This article describes a cell-based screening assay using an FITC-labeled CCR4 agonist (CKLF1-C27), a CKLF1 peptide fragment. Screening of our in-stock small-molecule library identified a 3-piperazinylcoumarin analogue 1 (IC(50) = 4.36 x 10(-6) M) that led to the discovery of orally active compound 41 (IC(50) = 2.12 x 10(-8) M) through systematic optimization. Compound 41 blocked the calcium mobilization and chemotaxis induced by CKLF1-C27 and reduced the asthmatic pathologic changes in lung tissue of human CKLF1-transfected mice. Further studies indicated that compound 41 ameliorated pathological changes via inhibition of the NF-kappaB signal pathway.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Asthmatic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents...,
http://linkedlifedata.com/resource/pubmed/chemical/CCR4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CKLF protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines,
http://linkedlifedata.com/resource/pubmed/chemical/Coumarins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CCR4
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1520-4804
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
25
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1741-54
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pubmed:meshHeading |
pubmed-meshheading:20099827-Administration, Oral,
pubmed-meshheading:20099827-Animals,
pubmed-meshheading:20099827-Anti-Asthmatic Agents,
pubmed-meshheading:20099827-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:20099827-Asthma,
pubmed-meshheading:20099827-Binding, Competitive,
pubmed-meshheading:20099827-Calcium,
pubmed-meshheading:20099827-Cell Line,
pubmed-meshheading:20099827-Chemokines,
pubmed-meshheading:20099827-Chemotaxis,
pubmed-meshheading:20099827-Coumarins,
pubmed-meshheading:20099827-Fibrosis,
pubmed-meshheading:20099827-High-Throughput Screening Assays,
pubmed-meshheading:20099827-Humans,
pubmed-meshheading:20099827-Lung,
pubmed-meshheading:20099827-Mice,
pubmed-meshheading:20099827-NF-kappa B,
pubmed-meshheading:20099827-Peptide Fragments,
pubmed-meshheading:20099827-Piperazines,
pubmed-meshheading:20099827-Radioligand Assay,
pubmed-meshheading:20099827-Receptors, CCR4,
pubmed-meshheading:20099827-Signal Transduction,
pubmed-meshheading:20099827-Structure-Activity Relationship
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pubmed:year |
2010
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pubmed:articleTitle |
Discovery and optimization of novel 3-piperazinylcoumarin antagonist of chemokine-like factor 1 with oral antiasthma activity in mice.
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pubmed:affiliation |
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 2 Nanwei Rd, Beijing 100050, PR China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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