Update on the status of DP2 receptor antagonists; from proof of concept through clinical failures to promising new drugs.
作者： Peter Norman
DOI: 10.1517/13543784.2013.839658
关键词:
摘要: Introduction: The identification of PGD2 as the cognate ligand for DP2 (formerly CRTH2) receptor and apparent role that in allergic disease has led to considerable interest development antagonists treatment asthma. Around 20 have progressed into development. Areas covered: clinical those whose been discontinued are discussed detail. This article highlights former examines available data respect both groups antagonists. It draws upon from trial registries well presented. Expert Opinion: unpromising outcomes obtained with setipiprant, vidupiprant AZD-1981, reason why OC-459 appears stalled, all considered. An assessment nine currently advantages ADC-3680 MK-1029. Th...
sci-hub.se 参考文章(49)
N. Barnes, I. Pavord, A. Chuchalin, J. Bell, M. Hunter, T. Lewis, D. Parker, M. Payton, L. Pearce Collins, R. Pettipher, J. Steiner, C. M. Perkins, A randomized, double‐blind, placebo‐controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma Clinical & Experimental Allergy. ,vol. 42, pp. 38- 48 ,(2012) , 10.1111/J.1365-2222.2011.03813.X
JA Schmidt, FM Bell, E Akam, C Marshall, IA Dainty, A Heinemann, IG Dougall, RV Bonnert, CA Sargent, Biochemical and pharmacological characterization of AZD1981, an orally available selective DP2 antagonist in clinical development for asthma. British Journal of Pharmacology. ,vol. 168, pp. 1626- 1638 ,(2013) , 10.1111/BPH.12053
Sue Snape, Caroline Patwell, David Singh, Salvatore Febbraro, Bharat Ruparelia, Mary Fitzgerald, Noel Snell, The safety, PK and PD profile of ADC3680, a potent and selective CRTh2 antagonist, in healthy volunteers and partly controlled atopic asthmatic subjects European Respiratory Journal. ,vol. 42, pp. 3401- ,(2013)
Miriam Andrés, Mónica Bravo, Maria Antonia Buil, Marta Calbet, Jordi Castro, Teresa Domènech, Peter Eichhorn, Manel Ferrer, Elena Gómez, Martin D. Lehner, Imma Moreno, Richard S. Roberts, Sara Sevilla, 2-(1H-Pyrazol-4-yl)acetic acids as CRTh2 antagonists Bioorganic & Medicinal Chemistry Letters. ,vol. 23, pp. 3349- 3353 ,(2013) , 10.1016/J.BMCL.2013.03.093
Peter J. Mauser, Aileen House, Howard Jones, Craig Correll, Christopher Boyce, Richard W. Chapman, Pharmacological characterization of the late phase reduction in lung functions and correlations with microvascular leakage and lung edema in allergen-challenged Brown Norway rats Pulmonary Pharmacology & Therapeutics. ,vol. 26, pp. 677- 684 ,(2013) , 10.1016/J.PUPT.2013.03.005
Anja Valdenaire, Julien Pothier, Dorte Renneberg, Markus A. Riederer, Oliver Peter, Xavier Leroy, Carmela Gnerre, Heinz Fretz, Evolution of novel tricyclic CRTh2 receptor antagonists from a (E)-2-cyano-3-(1H-indol-3-yl)acrylamide scaffold Bioorganic & Medicinal Chemistry Letters. ,vol. 23, pp. 944- 948 ,(2013) , 10.1016/J.BMCL.2012.12.050
Y-H Wang, M Trucksis, J J McElwee, P H Wong, C Maciolek, C D Thompson, T Prueksaritanont, G C Garrett, R Declercq, E Vets, K J Willson, R C Smith, J A Klappenbach, G J Opiteck, J A Tsou, C Gibson, T Laethem, P Panorchan, M Iwamoto, P M Shaw, J A Wagner, J C Harrelson, UGT2B17 genetic polymorphisms dramatically affect the pharmacokinetics of MK-7246 in healthy subjects in a first-in-human study. Clinical Pharmacology & Therapeutics. ,vol. 92, pp. 96- 102 ,(2012) , 10.1038/CLPT.2012.20
Mamoru Tasaki, Miki Kobayashi, Yoshiyuki Tenda, Susumu Tsujimoto, Shoko Nakazato, Mako Numazaki, Yasuno Hirano, Hiroshi Matsuda, Tadashi Terasaka, Yasuhiro Miyao, Yasuaki Shimizu, Yoshitaka Hirayama, Inhibition of antigen-induced airway inflammation and hyperresponsiveness in guinea pigs by a selective antagonist of "chemoattractant receptor homologous molecule expressed on Th2 cells" (CRTH2). European Journal of Pharmaceutical Sciences. ,vol. 49, pp. 434- 440 ,(2013) , 10.1016/J.EJPS.2013.04.017
Heather Giles, P. Leff, Mary L. Bolofo, M.G. Kelly, A.D. Robertson, The classification of prostaglandin DP‐receptors in platelets and vasculature using BW A868C, a novel, selective and potent competitive antagonist British Journal of Pharmacology. ,vol. 96, pp. 291- 300 ,(1989) , 10.1111/J.1476-5381.1989.TB11816.X
G. Bain, C. D. King, J. Brittain, J. P. Hartung, I. DeArmond, B. Stearns, Y. P. Truong, J. H. Hutchinson, J. F. Evans, K. Holme, Pharmacodynamics, Pharmacokinetics, and Safety of AM211: A Novel and Potent Antagonist of the Prostaglandin D2 Receptor Type 2 The Journal of Clinical Pharmacology. ,vol. 52, pp. 1482- 1493 ,(2012) , 10.1177/0091270011421912