Pharmacological characterization of a novel nonpeptide antagonist for formyl peptide receptor-like 1
文献类型：期刊论文
| 作者 | Zhou, Caihong; Zhang, Song; Nanamori, Masakatsu; Zhang, Yueyun; Liu, Qing; Li, Na; Sun, Meiling; Tian, Jun; Ye, Patrick P.; Cheng, Ni |
| 刊名 | MOLECULAR PHARMACOLOGY
 |
| 出版日期 | 2007-10 |
| 卷号 | 72期号:4页码:976-983 |
| ISSN号 | 0026-895X |
| DOI | 10.1124/mol.107.037564 |
| 文献子类 | Article |
| 英文摘要 | A series of quinazolinone derivatives were synthesized based on a hit compound identified from a high-throughput screening campaign targeting the human formyl peptide receptor-like 1 (FPRL1). Based on structure-activity relationship analysis, we found that substitution on the para position of the 2-phenyl group of the quinazolinone backbone could alter the pharmacological properties of the compound. The methoxyl substitution produced an agonist 4-butoxy-N-[2-(4-methoxy-phenyl)-4-oxo- 1,4-dihydro-2H-quinazolin-3-yl]-benzamide (Quin-C1;C1), whereas a hydroxyl substitution resulted in a pure antagonist, Quin-C7 (C7). Several partial agonists were derived from other substitutions on the para position. C7 partially displaced [I-125] Trp-Lys-Tyr-Met-Val-D-Met-NH2 (WKYMVm) binding to FPRL1 but not [H-3]N-formyl-Met-Leu-Phe to formyl peptide receptor. In functional assays using FPRL1-expressing RBL-2H3 cells, C7 inhibited calcium mobilization and chemotaxis induced by WKYMVm and C1 and degranulation elicited by C1. C7 also suppressed C1-induced extracellular signal-regulated kinase phosphorylation and reduced arachidonic acid-induced ear edema in mice. This study represents the first characterization of a nonpeptidic antagonist for FPRL1 and suggests the prospect of using low molecular weight compounds as modulators of chemoattractant receptors in vitro and in vivo. |
| WOS关键词 | PROTEIN-COUPLED RECEPTORS ; LIGAND-BINDING ; ACTIVATION ; IDENTIFICATION ; WKYMVM ; CELLS ; FPRL1 |
| 资助项目 | NIAID NIH HHS[AI033503] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000249561500018 |
| 出版者 | AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/273143]  |
| 专题 | 国家新药筛选中心 |
| 通讯作者 | Wang, Ming-Wei |
| 作者单位 | 1.Chinese Acad Sci, Grad Sch, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Natl Ctr Drug Screeing, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL USA |
| 推荐引用方式 GB/T 7714 | Zhou, Caihong,Zhang, Song,Nanamori, Masakatsu,et al. Pharmacological characterization of a novel nonpeptide antagonist for formyl peptide receptor-like 1[J]. MOLECULAR PHARMACOLOGY,2007,72(4):976-983. |
| APA | Zhou, Caihong.,Zhang, Song.,Nanamori, Masakatsu.,Zhang, Yueyun.,Liu, Qing.,...&Wang, Ming-Wei.(2007).Pharmacological characterization of a novel nonpeptide antagonist for formyl peptide receptor-like 1.MOLECULAR PHARMACOLOGY,72(4),976-983. |
| MLA | Zhou, Caihong,et al."Pharmacological characterization of a novel nonpeptide antagonist for formyl peptide receptor-like 1".MOLECULAR PHARMACOLOGY 72.4(2007):976-983. |
入库方式： OAI收割
来源：上海药物研究所
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