Antagonism of the prostaglandin D2 receptors DP1 and CRTH2 as an approach to treat allergic diseases

被引:255
作者
Pettipher, Roy
Hansel, Trevor T.
Armer, Richard
机构
[1] Oxagen Ltd, Abingdon OX14 4RY, Oxon, England
[2] Royal Brompton Hosp, Natl Heart & Lung Inst, Clin Studies Unit, London SW3 6HP, England
关键词
D O I
10.1038/nrd2266
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Immunological activation of mast cells is an important trigger in the cascade of inflammatory events leading to the manifestation of allergic diseases. Pharmacological studies using the recently discovered DP1 and CRTH2 antagonists combined with genetic analysis support the view that these receptors have a pivotal role in mediating aspects of allergic diseases that are resistant to current therapy. This Review focuses on the emerging roles that DP1 and CRTH2 ( also known as DP2) have in acute and chronic aspects of allergic diseases and proposes that, rather than having opposing actions, these receptors have complementary roles in the initiation and maintenance of the allergy state. We also discuss recent progress in the discovery and development of selective antagonists of these receptors.
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页码:313 / 325
页数:13
相关论文
共 134 条
[1]   Molecular cloning, chromosome mapping and characterization of the mouse CRTH2 gene, a putative member of the leukocyte chemoattractant receptor family [J].
Abe, H ;
Takeshita, T ;
Nagata, K ;
Arita, T ;
Endo, Y ;
Fujita, T ;
Takayama, H ;
Kubo, M ;
Sugamura, K .
GENE, 1999, 227 (01) :71-77
[2]   BAY u3405, a thromboxane A(2) antagonist, reduces bronchial hyperresponsiveness in asthmatics [J].
Aizawa, H ;
Shigyo, M ;
Nogami, H ;
Hirose, T ;
Hara, N .
CHEST, 1996, 109 (02) :338-342
[3]  
Ajuebor MN, 2000, AM J PHYSIOL-GASTR L, V279, pG238
[4]  
ALJARAD N, 1994, BRIT J CLIN PHARMACO, V37, P97
[5]   Activation of the D prostanoid receptor 1 regulates immune and skin allergic responses [J].
Angeli, W ;
Staumont, D ;
Charbonnier, AS ;
Hammad, H ;
Gosset, P ;
Pichavant, M ;
Lambrecht, BN ;
Capron, M ;
Dombrowicz, D ;
Trottein, F .
JOURNAL OF IMMUNOLOGY, 2004, 172 (06) :3822-3829
[6]  
Arimura A, 2001, J PHARMACOL EXP THER, V298, P411
[7]   Indole-3-acetic acid antagonists of the prostaglandin D2 receptor CRTH2 [J].
Armer, RE ;
Ashton, MR ;
Boyd, EA ;
Brennan, CJ ;
Brookfield, FA ;
Gazi, L ;
Gyles, SL ;
Hay, PA ;
Hunter, MG ;
Middlemiss, D ;
Whittaker, M ;
Xue, LZ ;
Pettipher, R .
JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (20) :6174-6177
[8]  
ASTRAZENECA AB, 2003, Patent No. 03101961
[9]  
ASTRAZENECA AB, 2003, Patent No. 03101981
[10]  
Awad M. M. A., 2004, World Pat., Patent No. [2004,035,543, 2004035543, WO 2004035543]