Prostaglandin D2 receptor antagonists in early development as potential therapeutic options for asthma

References

• Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) [Internet]. 2015 [cited 2016 Apr]. Available from: http://www.ginas-thma.org/
   Google Scholar
• Demoly P, Paggiaro P, Plaza V, et al. Prevalence of asthma control among adults in France, Germany, Italy, Spain and the UK. Eur Respir Rev. 2009;18:105–112.
   PubMedGoogle Scholar
• Bateman ED, Bousquet J, Busse WW, et al. Stability of asthma control with regular treatment: an analysis of the Gaining Optimal Asthma controL (GOAL) study. Allergy. 2008;63:932–938.
   PubMed Web of Science ®Google Scholar
• Reddel HK, Taylor DR, Bateman ED, et al. An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am J Respir Crit Care Med. 2009;180:59–99.
   PubMed Web of Science ®Google Scholar
• Chung KF, Wenzel SE, Brozek JL, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014;43:343–373.
   PubMed Web of Science ®Google Scholar
• Pettipher R, Hansel TT, Armer R. Antagonism of the prostaglandin D2 receptors DP1 and CRTH2 as an approach to treat allergic diseases. Nat Rev Drug Discov. 2007;6:313–325.
   PubMed Web of Science ®Google Scholar
• Samuelsson B, Goldyne NE, Granstrom E, et al. Prostaglandins and thromboxane. Annu Rev Biochem. 1978;47:997–1003.
   PubMed Web of Science ®Google Scholar
• Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem. 2000;69:145–182.
   PubMed Web of Science ®Google Scholar
• Ford-Hutchinson A, Gresser M, Young R. 5-Lipoxygenase. Annu Rev Biochem. 1994;63:383–417.
   PubMed Web of Science ®Google Scholar
• Kuhn H, Thiele BJ. Arachidonate 15-lipoxygenase. J Lipid Mediat Cell Signal. 1995;12:157–170.
   PubMedGoogle Scholar
• Centanni S, Santus P, Di Marco F, et al. The potential role of tocopherol in asthma and allergies. Modification of the leukotriene pathway. BioDrugs. 2001;15:81–86.
   PubMed Web of Science ®Google Scholar
• Liu MC, Dubé LM, Lancaster J, et al. Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. J Allergy Clin Immunol. 1996;98:859–871.
   PubMed Web of Science ®Google Scholar
• Kp H, Barnes NC. Lung function improvement in asthma with a cysteinyl-leukotriene receptor antagonist. Lancet. 1991;337:1062–1063.
   PubMed Web of Science ®Google Scholar
• Monneret G, Li H, Vasilescu J, et al. 15-Deoxy-Δ12, 14-prostaglandins D2 and J2 are potent activators of human eosinophils. J Immunol. 2002;168:3563–3569.
   PubMed Web of Science ®Google Scholar
• Matsuoka T, Hirata M, Tanaka H, et al. Prostaglandin D2 as a mediator of allergic asthma. Science. 2000;287:2013–2017.
   PubMed Web of Science ®Google Scholar
• Gazi L, Gyles S, Rose J, et al. Δ12-prostaglandin D2 is a potent and selective CRTH2 receptor agonist and causes activation of human eosinophils and Th2 lymphocytes. Prostaglandins Other Lipid Mediat. 2005;75:153–167.
   PubMed Web of Science ®Google Scholar
• Sandig H, Andrew D, Barnes A, et al. 9α, 11β-PGF2 and its stereoisomer PGF2α are novel agonists of the chemoattractant receptor, CRTH2. FEBS Lett. 2006;580:373–379.
   PubMed Web of Science ®Google Scholar
• Xue L, Gyles SL, Wettey FR, et al. Prostaglandin D2 causes preferential induction of proinflammatory Th2 cytokine production through an action on chemoattractant receptor-like molecule expressed on Th2 cells. J Immunol. 2005;175:6531–6536.
   PubMed Web of Science ®Google Scholar
• Moore ML, Peebles RS. Update on the role of prostaglandins in allergic lung inflammation: separating friends from foes, harder than you might think. J Allergy Clin Immunol. 2006;117:1036–1039.
   PubMed Web of Science ®Google Scholar
• Nagata K, Hirai H. The second PGD(2) receptor CRTH2: structure, properties, and functions in leukocytes. Prostaglandins Leukot Essent Fatty Acids. 2003;69:169–177.
   PubMed Web of Science ®Google Scholar
• Hirai H, Tanaka K, Yoshie O, et al. Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2. J Exp Med. 2001;193:255–261.
   PubMed Web of Science ®Google Scholar
• Chang JE, Doherty TA, Baum R, et al. Prostaglandin D2 regulates human type 2 innate lymphoid cell chemotaxis. J Allergy Clin Immunol. 2014;133:899–901.
   PubMed Web of Science ®Google Scholar
• Palikhe NS, Laratta C, Nahirney D, et al. Elevated levels of circulating CD4(+) CRTh2(+) T cells characterize severe asthma. Clin Exp Allergy. 2016;46:825–836.
   PubMed Web of Science ®Google Scholar
• Heinemann A, Schuligoi R, Sabroe I, et al. Δ12-prostaglandin J2, a plasma metabolite of prostaglandin D2, causes eosinophil mobilization from the bone marrow and primes eosinophils for chemotaxis. J Immunol. 2003;170:4752–4758.
   PubMed Web of Science ®Google Scholar
• Stinson SE, Amrani Y, Brightling CE. D prostanoid receptor 2 (chemoattractant receptor-homologous molecule expressed on TH2 cells) protein expression in asthmatic patients and its effects on bronchial epithelial cells. J Allergy Clin Immunol. 2015;135:395–406.
   PubMed Web of Science ®Google Scholar
• Wojno ED, Monticelli LA, Tran SV, et al. The prostaglandin D₂ receptor CRTH2 regulates accumulation of group 2 innate lymphoid cells in the inflamed lung. Mucosal Immunol. 2015;8:1313–1323.
   PubMed Web of Science ®Google Scholar
• Schuligoi R, Sturm E, Luschnig P, et al. CRTH2 and D-type prostanoid receptor antagonists as novel therapeutic agents for inflammatory diseases. Pharmacology. 2010;85:372–382.
   PubMed Web of Science ®Google Scholar
• Nagata K, Hirai H, Tanaka K, et al. CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s). FEBS Lett. 1999;459:195–199.
   PubMed Web of Science ®Google Scholar
• Jandl K, Stacher E, Bálint Z, et al. Activated prostaglandin D2 receptors on macrophages enhance neutrophil recruitment into the lung. J Allergy Clin Immunol. 2016;137:833–843.
   PubMed Web of Science ®Google Scholar
• Shiraishi Y, Asano K, Nakajima T, et al. Prostaglandin D2-induced eosinophilic airway inflammation is mediated by CRTH2 receptor. J Pharmacol Exp Ther. 2005;312:954–960.
   PubMed Web of Science ®Google Scholar
• Uller L, Mathiesen JM, Alenmyr L, et al. Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation. Respir Res. 2007;8:16.
   PubMed Web of Science ®Google Scholar
• Lukacs NW, Berlin AA, Franz-Bacon K, et al. CRTH2 antagonism significantly ameliorates airway hyperreactivity and downregulates inflammation-induced genes in a mouse model of airway inflammation. Am J Physiol Lung Cell Mol Physiol. 2008;295:L767–L779.
   PubMed Web of Science ®Google Scholar
• Sally E, Stinson MS, Amrani Y, et al. D prostanoid receptor 2 (chemoattractant receptor–homologous molecule expressed on TH2 cells) protein expression in asthmatic patients and its effects on bronchial epithelial cells. J Allergy Clin Immunol. 2015;135:395–406.
   PubMed Web of Science ®Google Scholar
• Schleimer RP, Fox CC, Naclerio RM, et al. Role of human basophils and mast cells in the pathogenesis of allergic diseases. J Allergy Clin Immunol. 1985;76:369–374.
   PubMed Web of Science ®Google Scholar
• Anhut H, Peskar BA, Bernauer W. Release of 15-keto-13,14-dihydro-thromboxane B 2 and prostaglandin D 2 during anaphylaxis as measured by radioimmunoassay. Naunyn Schmiedebergs Arch Pharmacol. 1978;305:247–252.
   PubMed Web of Science ®Google Scholar
• Vinall SL, Townsend ER, Pettipher R. A paracrine role for chemoattractant receptor homologous molecule expressed on T helper type 2 cells (CRTH2) in mediating chemotactic activation of CRTH2+CD4+ T helper type 2 lymphocytes. Immunology. 2007;121:577–584.
   PubMed Web of Science ®Google Scholar
• Tajima T, Murata T, Aritake K, et al. Lipopolysaccharide induces macrophage migration via prostaglandin D2 and prostaglandin E2. J Pharmacol Exp Ther. 2008;326:493–501.
   PubMed Web of Science ®Google Scholar
• Söderström M, Wigren J, Surapureddi S, et al. Novel prostaglandinD2-derived activators of peroxisome proliferator-activated receptor-gamma are formed in macrophage cell cultures. Biochim Biophys Acta. 2003;1631:35–41.
   PubMed Web of Science ®Google Scholar
• Hyo S, Kawata R, Kadoyama K, et al. Expression of prostaglandin D 2 synthase in activated eosinophils in nasal polyps. Arch Otolaryngol Head Neck Surg. 2007;133:693–700.
   PubMedGoogle Scholar
• Fujitani Y, Kanaoka Y, Aritake K, et al. Pronounced eosinophilic lung inflammation and Th2 cytokine release in human lipocalin-type prostaglandin D synthase transgenic mice. J Immunol. 2002;168:443–449.
   PubMed Web of Science ®Google Scholar
• O’Byrne PM. Leukotrienes in the pathogenesis of asthma. Chest. 1997;111:27S–34S.
   PubMed Web of Science ®Google Scholar
• Woerly G, Roger N, Loiseau S, et al. Expression of Th1 and Th2 immunoregulatory cytokines by human eosinophils. Int Arch Allergy Immunol. 1999;118:95–97.
   PubMed Web of Science ®Google Scholar
• Aceves SS, Broide DH. Airway fibrosis and angiogenesis due to eosinophil trafficking in chronic asthma. Curr Mol Med. 2008;8:350–358.
   PubMed Web of Science ®Google Scholar
• Robinson D, Hamid Q, Bentley A, et al. Activation of CD4+ T cells, increased Th2-type cytokine mRNA expression, and eosinophil recruitment in bronchoalveolar lavage after allergen inhalation challenge in patients with atopic asthma. J Allergy Clin Immunol. 1993;92:313–324.
   PubMed Web of Science ®Google Scholar
• Corrigan CJ, Hamid Q, North J, et al. Peripheral blood CD4 but not CD8 T lymphocytes in patients with exacerbation of asthma transcribe and translate messenger RNA encoding cytokines which prolong eosinophil survival in the context of a Th2-type pattern: effect of glucocorticoid therapy. Am J Respir Cell Mol Biol. 1995;12:567–578.
   PubMed Web of Science ®Google Scholar
• Robinson DS, Hamid Q, Ying S, et al. Predominant Th2-like bronchoalveolar T lymphocyte population in atopic asthma. N Engl J Med. 1992;326:298–304.
   PubMed Web of Science ®Google Scholar
• Murray JJ, Tonnel AB, Brash AR, et al. Release of prostaglandin D2 into human airways during acute antigen challenge. N Engl J Med. 1986;315:800–804.
   PubMed Web of Science ®Google Scholar
• Liu MC, Bleecker ER, Lichtenstein LM. Evidence for elevated levels of histamine prostaglandin D2, and other bronchoconstricting prostaglandins in the airways of subjects with mild asthma. Am Rev Respir Dis. 1990;142:126–132.
   PubMed Web of Science ®Google Scholar
• Wenzel SE, Westcott JY, Larsen GL. Bronchoalveolar lavage fluid mediator levels 5 minutes after allergen challenge in atopic subjects with asthma: relationship to the development of late asthmatic responses. J Allergy Clin Immunol. 1991;87:540–548.
   PubMed Web of Science ®Google Scholar
• Fajt ML, Gelhaus SL, Freeman B, et al. Prostaglandin D2 pathway upregulation: relation to asthma severity, control, and TH2 inflammation. J Allergy Clin Immunol. 2013;131:1504–1512.
   PubMed Web of Science ®Google Scholar
• Dahl R. Systemic side effects of inhaled corticosteroids in patients with asthma. Respir Med. 2006;100:1307–1317.
   PubMed Web of Science ®Google Scholar
• Holgate ST. Pathophysiology of asthma: what has our current understanding taught us about new therapeutic approaches? J Allergy Clin Immunol. 2011;128:495–505.
   PubMed Web of Science ®Google Scholar
• Norman P. Update on the status of DP2 receptor antagonists; from proof of concept through clinical failures to promising new drugs. Expert Opin Investig Drugs. 2014;23:55–66.
   PubMed Web of Science ®Google Scholar
• Crosignani S, Page P, Missotten M, et al. Discovery of a new class of potent, selective, and orally bioavailable CRTH2 (DP2) receptor antagonists for the treatment of allergic inflammatory diseases. J Med Chem. 2008;51:2227–2243.
   PubMed Web of Science ®Google Scholar
• Crosignani S, Jorand-Lebrun C, Page P, et al. Optimization of the central core of indolinone-acetic acid-based CRTH2 (DP2) receptor antagonists. ACS Med Chem Lett. 2011;2:644–649.
   PubMed Web of Science ®Google Scholar
• Uller L, Mosolff Mathiesen J, Alenmyr L, et al. Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation. Respir Res. 2007;8:16.
   PubMed Web of Science ®Google Scholar
• Pettipher R, Vinall SL, Xue L, et al. Pharmacologic profile of OC000459, a potent, selective, and orally active D prostanoid receptor 2 antagonist that inhibits mast cell-dependent activation of T helper 2 lymphocytes and eosinophils. J Pharmacol Exp Ther. 2012;340:473–482.
   PubMed Web of Science ®Google Scholar
• Nishikawa-Shimono R, Sekiguchi Y, Kawamura M, et al. Isoquinoline derivatives as potent, selective, and orally active CRTH2 antagonists. Chem Pharm Bull. 2014;62:528–537.
   PubMed Web of Science ®Google Scholar
• Gil MA, Caniga M, Woodhouse LD, et al. Anti-inflammatory actions of chemoattractant receptor-homologous molecule expressedonTh2 by the antagonist MK-7246 in a novel rat model of Alternaria alternata elicited pulmonary inflammation. Eur J Pharmacol. 2014;743:106–116.
   PubMed Web of Science ®Google Scholar
• Calbet M, Andrés M, Armengol C, et al. Pharmacological characterization of CRTh2 antagonist LAS191859: long receptor residence time translates into long-lasting in vivo efficacy. Pharmacol Res. 2016 Jun 15. pii: S1043-6618(16)30144-X. doi:10.1016/j.phrs.2016.06.014. [Epub ahead of print].
   PubMedGoogle Scholar
• Barnes N, Pavord I, Chuchalin A, et al. A randomized, double-blind, placebo-controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma. Clin Exp Allergy. 2012;42:38–48.
   PubMed Web of Science ®Google Scholar
• Singh D, Cadden P, Hunter M, et al. Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459. Eur Respir J. 2013;41:46–52.
   PubMed Web of Science ®Google Scholar
• Pettipher R, Hunter MG, Perkins CM, et al. Heightened response of eosinophilic asthmatic patients to the CRTH2 antagonist OC000459. Allergy. 2014;69:1223–1232.
   PubMed Web of Science ®Google Scholar
• Busse WW, Wenzel SE, Meltzer EO, et al. Safety and efficacy of the prostaglandin D2 receptor antagonist AMG 853 in asthmatic patients. J Allergy Clin Immunol. 2013;131:339–345.
   PubMed Web of Science ®Google Scholar
• Diamant Z, Sidharta PN, Singh D, et al. Setipiprant, a selective CRTH2 antagonist, reduces allergen-induced airway responses in allergic asthmatics. Clin Exp Allergy. 2014;44:1044–1052.
   PubMed Web of Science ®Google Scholar
• Hall IP, Fowler AV, Gupta A, et al. Efficacy of BI 671800, an oral CRTH2 antagonist, in poorly controlled asthma as sole controller and in the presence of inhaled corticosteroid treatment. Pulm Pharmacol Ther. 2015;32:37–44.
   PubMed Web of Science ®Google Scholar
• Erpenbeck VJ, Vets E, Gheyle L, et al. Pharmacokinetics, safety, and tolerability of fevipiprant (QAW039), a novel CRTh2 receptor antagonist: results from 2 randomized, phase 1, placebo-controlled studies in healthy volunteers. Clin Pharmacol Drug Dev. 2016;5:306–313.
   PubMed Web of Science ®Google Scholar
• Gonem S, Berair R, Singapuri A, et al. Late-breaking abstract: phase 2a randomized placebo-controlled trial of the oral prostaglandin D2 receptor (DP2/CRTh2) antagonist QAW039 in eosinophilic asthma. Eur Respir J. 2014;44(Suppl 58):2908.
   Google Scholar
• Erpenbeck VJ, Todor A, Popov S, et al. QAW039 (fevipiprant) improves lung function and control of asthma symptoms in patients with more severe air flow limitation: a proof-of-concept study. Eur Respir J. 2015;46(Suppl 59):2125.
   Google Scholar
• Wenzel S, Chantry D, Eberhardt C, et al. ARRY-502, a potent, selective, oral CRTh2 antagonist reduces Th2 mediators in patients with mild to moderate Th2-driven asthma. Eur Respir J. 2014;44(Suppl.58):4836.
   Google Scholar