5-7-dihydroxy-4-methylcoumarin has been researched along with Asthma* in 1 studies
1 other study(ies) available for 5-7-dihydroxy-4-methylcoumarin and Asthma
| Article | Year |
|---|---|
Discovery and optimization of novel 3-piperazinylcoumarin antagonist of chemokine-like factor 1 with oral antiasthma activity in mice.
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. Topics: Administration, Oral; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Binding, Competitive; Calcium; Cell Line; Chemokines; Chemotaxis; Coumarins; Fibrosis; High-Throughput Screening Assays; Humans; Lung; MARVEL Domain-Containing Proteins; Mice; NF-kappa B; Peptide Fragments; Piperazines; Radioligand Assay; Receptors, CCR4; Signal Transduction; Structure-Activity Relationship | 2010 |