Investigational prostaglandin D₂ receptor antagonists for airway inflammation

References

• Skloot GS. Asthma phenotypes and endotypes: a personalized approach to treatment. Curr Opin Pulm Med. 2016;22(1):3–9.
   PubMed Web of Science ®Google Scholar
• Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention updated [Internet]. 2015 [cited March 1 2016]. Available from: www.ginasthma.org.
   Google Scholar
• Montuschi P, Barnes PJ. New perspectives in pharmacological treatment of mild persistent asthma. Drug Discov Today. 2011;16(23–24):1084–1091.
   PubMed Web of Science ®Google Scholar
• Nguyen TH, Casale TB. Immune modulation for treatment of allergic disease. Immunol Rev. 2011;242(1):258–271.
   PubMed Web of Science ®Google Scholar
• Oguma T, Asano K, Ishizaka A. Role of prostaglandin D2 and its receptors in the pathophysiology of asthma. Allergol Int. 2008;57(4):307–312.
   PubMedGoogle Scholar
• Arima M, Fukuda T. Prostaglandin D2 receptors DP and CRTH2 in the pathogenesis of asthma. Curr Mol Med. 2008;8(5):365–375.
   PubMed Web of Science ®Google Scholar
• Tait 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(6):1313–1323.
   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(1):55–66.
   PubMed Web of Science ®Google Scholar
• Townley RG, Agrawal S. CRTH2 antagonists in the treatment of allergic responses involving TH2 cells, basophils, and eosinophils. Ann Allergy Asthma Immunol. 2012;109(6):365–374.
   PubMed Web of Science ®Google Scholar
• Pettipher R, Whittaker M. Update on the development of antagonists of chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2). From lead optimization to clinical proof-of-concept in asthma and allergic rhinitis. J Med Chem. 2012;55(7):2915–2931.
   PubMed Web of Science ®Google Scholar
• Shiraishi Y, Asano K, Niimi K, et al. Cyclooxygenase-2/prostaglandin D2/CRTH2 pathway mediates double-stranded RNA-induced enhancement of allergic airway inflammation. J Immunol. 2008;180(1):541–549.
   PubMed Web of Science ®Google Scholar
• Carey MA, Germolec DR, Langenbach R, et al. Cyclooxygenase enzymes in allergic inflammation and asthma. Prostaglandins Leukot Essent Fatty Acids. 2003;69(2–3):157–162.
   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
• Oguma T, Asano K, Ishizaka A. Role of prostaglandin D2 and its receptors in the pathophysiology of asthma. Allergol Int. 2008;57:307–312.
   PubMedGoogle Scholar
• Dichlberger A, Schlager S, Kovanen PT, et al. Lipid droplets in activated mast cells - a significant source of triglyceride-derived arachidonic acid for eicosanoid production. Eur J Pharmacol. 2015 Jul 9. pii: S0014-2999(15)30149-7.
   PubMedGoogle 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
• 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(4):313–325.
   PubMed Web of Science ®Google Scholar
• Bochenek G, Nizankowska E, Gielicz A, et al. Plasma 9alpha,11beta-PGF2, a PGD2 metabolite, as a sensitive marker of mast cell activation by allergen in bronchial asthma. Thorax. 2004;59(6):459–464.
   PubMed Web of Science ®Google Scholar
• Chen JJ, Budelsky AL. Prostaglandin D2 receptor CRTH2 antagonists for the treatment of inflammatory diseases. Prog Med Chem. 2011;50:49–107.
   PubMedGoogle Scholar
• Kiriyama M, Ushikubi F, Kobayashi T, et al. Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1997;122(2):217–224.
   PubMed Web of Science ®Google Scholar
• Lilly CM, Palmer LJ. The role of prostaglandin D receptor gene in asthma pathogenesis. Am J Respir Cell Mol Biol. 2005;33(3):224–226.
   PubMed Web of Science ®Google Scholar
• García-Solaesa V, Sanz-Lozano C, Padrón-Morales J, et al. The prostaglandin D2 receptor (PTGDR) gene in asthma and allergic diseases. Allergol Immunopathol (Madr). 2014;42(1):64–68.
   PubMed Web of Science ®Google Scholar
• Hirano Y, Shichijo M, Ikeda M, et al. Prostanoid DP receptor antagonists suppress symptomatic asthma-like manifestation by distinct actions from a glucocorticoid in rats. Eur J Pharmacol. 2011;666(1–3):233–241.
   PubMed Web of Science ®Google Scholar
• Boie Y, Sawyer N, Slipetz DM, et al. Molecular cloning and characterization of the human prostanoid DP receptor. J Biol Chem. 1995;270(32):18910–18916.
   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(2):255–261.
   PubMed Web of Science ®Google Scholar
• Moon TC, Campos-Alberto E, Yoshimura T, et al. Expression of DP2 (CRTh2), a prostaglandin D2 receptor, in human mast cells. PLoS One. 2014;9:e108595.
   PubMed Web of Science ®Google Scholar
• Jones RL, Giembycz MA, Woodward DF. Prostanoid receptor antagonists: development strategies and therapeutic applications. Br J Pharmacol. 2009;158(1):104–145.
   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(2–3):169–177.
   PubMed Web of Science ®Google Scholar
• Nagata K, Tanaka K, Ogawa K, et al. Selective expression of a novel surface molecule by human Th2 cells in vivo. J Immunol. 1999;162(3):1278–1286.
   PubMed Web of Science ®Google Scholar
• Sandig H, Andrew D, Barnes AA, et al. 9α,11β-PGF2 and its stereoisomer PGF2α are novel agonists of the chemoattractant receptor, CRTH2. FEBS Lett. 2006;580(2):373–379.
   PubMed Web of Science ®Google Scholar
• Xue L, Barrow A, Pettipher R. Novel function of CRTH2 in preventing apoptosis of human Th2 cells through activation of the phosphatidylinositol 3-kinase pathway. J Immunol. 2009;182(12):7580–7586.
   PubMed Web of Science ®Google Scholar
• Pettipher R. The roles of the prostaglandin D2 receptors DP1 and CRTH2 in promoting allergic responses. Br J Pharmacol. 2008;153(Suppl 1):191–199.
   PubMed Web of Science ®Google Scholar
• Van Hecken A, Depré M, De Lepeleire I, et al. The effect of MK-0524, a prostaglandin D2 receptor antagonist, on prostaglandin D2-induced nasal airway obstruction in healthy volunteers. Eur J Clin Pharmacol. 2007;63(2):135–141.
   PubMed Web of Science ®Google Scholar
• Nantel F, Fong C, Lamontagne S, et al. Expression of prostaglandin D synthase and the prostaglandin D2 receptors DP and CRTH2 in human nasal mucosa. Prostaglandins Other Lipid Mediat. 2004;73(1–2):87–101.
   PubMed Web of Science ®Google Scholar
• Choi YH, Lee S-N, Aoyagi H, et al. The extracellular signal-regulated kinase mitogen-activated protein kinase/ribosomal S6 protein kinase 1 cascade phosphorylates cAMP response element-binding protein to induce MUC5B gene expression via D-prostanoid receptor signaling. J Biol Chem. 2011;286(39):34199–34214.
   PubMed Web of Science ®Google Scholar
• Maher SA, Birrell MA, Adcock JJ, et al. Prostaglandin D2 and the role of the DP1, DP2 and TP receptors in the control of airway reflex events. Eur Respir J. 2015;45(4):1108–1118.
   PubMed Web of Science ®Google Scholar
• Takahashi G, Asanuma F, Suzuki N, et al. Effect of the potent and selective DP1 receptor antagonist, asapiprant (S-555739), in animal models of allergic rhinitis and allergic asthma. Eur J Pharmacol. 2015;765:15–23.
   PubMed Web of Science ®Google Scholar
• Arimura A, Yasui K, Kishino J, et al. Prevention of allergic inflammation by a novel prostaglandin receptor antagonist, S-5751. J Pharmacol Exp Ther. 2001;298(2):411–419.
   PubMed Web of Science ®Google Scholar
• Mitsumori S, Tsuri T, Honma T, et al. Synthesis and biological activity of various derivatives of a novel class of potent, selective, and orally active prostaglandin D2 receptor antagonists. 2. 6,6-Dimethylbicyclo[3.1.1]heptane derivatives. J Med Chem. 2003;46(12):2446–2455.
   PubMed Web of Science ®Google Scholar
• Shionogi discontinues development of S-5751, a prostaglandin D₂ receptor antagonist; [cited 2016 March 1]. Available from: http://www.shionogi.co.jp/en/company/news/2006/pmrltj0000001d4d.html..
   Google Scholar
• Hirano Y, Shichijo M, Deguchi M, et al. Synergistic effect of PGD2 via prostanoid DP receptor on TNF-α-induced production of MCP-1 and IL-8 in human monocytic THP-1 cells. Eur J Pharmacol. 2007;560(1):81–88.
   PubMed Web of Science ®Google Scholar
• Clinicaltrial.gov: home; [cited 2016 Mar 1]. Available from: www.clinicaltrials.gov.
   Google Scholar
• Sturino CF, O’Neill G, Lachance N, et al. Discovery of a potent and selective prostaglandin D2 receptor antagonist, [(3R)-4-(4-chloro-benzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl]-acetic acid (MK-0524). J Med Chem. 2007;50(4):794–806.
   PubMed Web of Science ®Google Scholar
• Philip G, Van Adelsberg J, Loeys T, et al. Clinical studies of the DP1 antagonist laropiprant in asthma and allergic rhinitis. J Allergy Clin Immunol. 2009;124(5):942–948.
   PubMed Web of Science ®Google Scholar
• Krug N, Gupta A, Badorrek P, et al. Efficacy of the oral chemoattractant receptor homologous molecule on TH2 cells antagonist BI 671800 in patients with seasonal allergic rhinitis. J Allergy Clin Immunol. 2014;133(2):414–419.
   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
• Miller D, LaForce C, Finn A, et al. Efficacy and safety of BI 671800, an oral CRTH2 antagonist, as add on therapy in poorly controlled asthma patients prescribed an inhaled corticosteroid. Eur Respir J. 2012;40(Suppl 56):P3085.
   Google Scholar
• Bain G, Lorrain DS, Stebbins KJ, et al. Pharmacology of AM211, a potent and selective prostaglandin D2 receptor type 2 antagonist that is active in animal models of allergic inflammation. J Pharmacol Exp Ther. 2011;338(1):290–301.
   PubMed Web of Science ®Google Scholar
• Bain G, King CD, Brittain J, et al. Pharmacodynamics, pharmacokinetics, and safety of AM211: a novel and potent antagonist of the prostaglandin D2 receptor type 2. J Clin Pharmacol. 2012;52(10):1482–1493.
   PubMed Web of Science ®Google Scholar
• Norman P. A novel DP2 receptor antagonist (AM-461): a patent evaluation of WO2011085033. Expert Opin Ther Pat. 2011;21(12):1931–1936.
   PubMed Web of Science ®Google Scholar
• Burgess L, Eberhardt C, Wright D, et al. Potent, selective, and orally active CRTh2 antagonists for allergic disease. Inflamm Res. 2011;60(Suppl 1):S284.
   Google Scholar
• Arry-502. Target CRTh2. Indication: asthma; [cited 2016 Mar 1]. Available from: http://www.arraybiopharma.com/product-pipeline/other-compounds/arry-502/.
   Google Scholar
• Bell S, Neitzel A, Nugent C, et al. ARRY-502: safety, PK and PD of the CRTH2 antagonist in healthy subjects following repeat dose administration. Am J Respir Crit Care Med. 2012;185:A2756.
   Google Scholar
• Wenzel SE, Hopkins R, Saunders M, et al. Safety and efficacy of ARRY-502, a potent, selective, oral CRTh2 antagonist, in patients with mild to moderate Th2-driven asthma. J Allergy Clin Immunol. 2014;133(2):AB4.
   Web of Science ®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):P4836.
   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(2):473–482.
   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(1):46–52.
   PubMed Web of Science ®Google 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(1):38–48.
   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(9):1223–1232.
   PubMed Web of Science ®Google Scholar
• Horak F, Zieglmayer P, Zieglmayer R, et al. The CRTH2 antagonist OC000459 reduces nasal and ocular symptoms in allergic subjects exposed to grass pollen, a randomised, placebo-controlled, double-blind trial. Allergy. 2012;67(12):1572–1579.
   PubMed Web of Science ®Google Scholar
• Sandham DA, Arnold N, Aschauer H, et al. Discovery and characterization of NVP-QAV680, a potent and selective CRTh2 receptor antagonist suitable for clinical testing in allergic diseases. Bioorg Med Chem. 2013;21(21):6582–6591.
   PubMed Web of Science ®Google Scholar
• Willard L, Brown Z, Owen C, et al. Characterization of QAW039 and QAV680, two novel, potent and selective CRTh2 antagonists. Eur Respir J. 2014;44(Suppl_58):P4072.
   Google Scholar
• Sykes D, Bradley M, Riddy D, et al. QAW039, a slowly dissociating CRTh2 antagonist with the potential for improved clinical efficacy. Mol Pharmacol. 2016;89(5):593–605.
   PubMedGoogle Scholar
• Sandham DA, Charlton SJ, Dubois G, et al. Discovery and characterisation of CRTh2 receptor antagonists suitable for clinical testing in allergic diseases. American Chemical Society Division of Medicinal Chemistry 248th ACS National Meeting, San Francisco (USA), 2014 Aug 10–14, abstract MEDI 349.
   Google Scholar
• Luu VT, Goujon J-Y, Meisterhans C, et al. Synthesis of a high specific activity methyl sulfone tritium isotopologue of fevipiprant (NVP-QAW039). J Labelled Comp Radiopharm. 2015;58(5):188–195.
   PubMed Web of Science ®Google Scholar
• Sykes DA, Dowling MR, Charlton SJ. Exploring the mechanism of agonist efficacy: a relationship between efficacy and agonist dissociation rate at the muscarinic M3 receptor. Mol Pharmacol. 2009;76(3):543–551.
   PubMed Web of Science ®Google Scholar
• Erpenbeck VJ, Vets E, Gheyle L, et al. Safety, tolerability, and pharmacokinetics of an oral competitive reversibile CRTh2 antagonist, QAW039, in healthy subjects. Eur Respir J. 2014;44(Suppl_58):P4073.
   Google Scholar
• Erpenbeck VJ, Popov TA, Miller SD, 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):PA2125.
   Google Scholar
• Berair R, Gonem S, Singapuri A, et al. Effect of QAW039, an oral prostaglandin D2 receptor (DP2/CRTh2) antagonist, upon sputum and bronchial eosinophilic inflammation and clinical outcomes in treatment-resistant asthma: a phase 2a randomized placebo-controlled trial. Am J Respir Crit Care Med. 2015;191:A6361.
   Google Scholar
• Berair R, Gonem S, Singapuri A, et al. Effect of QAW039, an oral prostaglandin D2 receptor (DP2/CRTh2) antagonist, upon bronchial epithelial integrity in treatment-resistant asthma in a randomized, placebo controlled study. Eur Respir J. 2015;46(Suppl 59):OA290.
   Google Scholar
• Astrazeneca: pipeline; [cited 2016 Mar 1]. Available from: https://www.astrazeneca.com/our-science/pipeline.html.
   Google Scholar
• Luker T, Bonnert R, Brough S, et al. Substituted indole-1-acetic acids as potent and selective CRTh2 antagonists-discovery of AZD1981. Bioorg Med Chem Lett. 2011;21(21):6288–6292.
   PubMed Web of Science ®Google Scholar
• Schmidt JA, Bell FM, Akam E, et al. Biochemical and pharmacological characterization of AZD1981, an orally available selective DP2 antagonist in clinical development for asthma. Br J Pharmacol. 2013;168(7):1626–1638.
   PubMed Web of Science ®Google Scholar
• Cook D, Brown D, Alexander R, et al. Lessons learned from the fate of AstraZeneca’s drug pipeline: a five-dimensional framework. Nat Rev Drug Discov. 2014;13(6):419–431.
   PubMed Web of Science ®Google Scholar
• Fretz H, Valdenaire A, Pothier J, et al. Identification of 2-(2-(1-naphthoyl)-8-fluoro-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)acetic acid (setipiprant/ACT-129968), a potent, selective, and orally bioavailable chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonist. J Med Chem. 2013;56(12):4899–4911.
   PubMed Web of Science ®Google Scholar
• Actelion provides update on CRTh2 program; [cited 2016 Mar 1]. Available from: http://www1.actelion.com/en/our-company/news-and-events.page?newsId=1598979.
   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(8):1044–1052.
   PubMed Web of Science ®Google Scholar
• Géhin M, Strasser DS, Zisowsky J, et al. A novel CRTH2 antagonist: single- and multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ACT-453859 in healthy subjects. J Clin Pharmacol. 2015;55(7):787–797.
   PubMed Web of Science ®Google Scholar
• Ito S, Terasaka T, Zenkoh T, et al. Discovery of novel and potent CRTH2 antagonists. Bioorg Med Chem Lett. 2012;22(2):1194–1197.
   PubMed Web of Science ®Google Scholar
• Tasaki M, Kobayashi M, Tenda Y, et al. 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). Eur J Pharm Sci. 2013;49(3):434–440.
   PubMed Web of Science ®Google Scholar
• Fitzgerald MF, Whitmarsh M, Prosser J, et al. The in vitro profile of ADC3680, a potent and selective CRTH2 antagonist for the treatment of inadequately controlled asthma. Am J Respir Crit Care Med. 2013;187:A2617.
   Web of Science ®Google Scholar
• Fitzgerald MF, Snape S, Febbraro S, et al. The safety, PK, and PD profile of ADC3680, a potent and selective CRTH2 antagonist, in healthy volunteers and partly controlled atopic asthmatic subjects. Am J Respir Crit Care Med. 2013;187:A3874.
   Google Scholar
• Low dose, once-daily oral CRTh2 antagonist; [cited 2016 Mar 1]. Available from: http://www.pulmagen.com/adc3680.html
   Google Scholar
• Simard D, Leblanc Y, Berthelette C, et al. Azaindoles as potent CRTH2 receptor antagonists. Bioorg Med Chem Lett. 2011;21(2):841–845.
   PubMed Web of Science ®Google Scholar
• Gallant M, Beaulieu C, Berthelette C, et al. Discovery of MK-7246, a selective CRTH2 antagonist for the treatment of respiratory diseases. Bioorg Med Chem Lett. 2011;21(1):288–293.
   PubMed Web of Science ®Google Scholar
• Molinaro C, Bulger PG, Lee EE, et al. CRTH2 antagonist MK-7246: a synthetic evolution from discovery through development. J Org Chem. 2012;77(5):2299–2309.
   PubMed Web of Science ®Google Scholar
• Gervais FG, Sawyer N, Stocco R, et al. Pharmacological characterization of MK-7246, a potent and selective CRTH2 (chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells) antagonist. Mol Pharmacol. 2011;79(1):69–76.
   PubMed Web of Science ®Google Scholar
• Mauser PJ, House A, Jones H, et al. Pharmacological characterization of the late phase reduction in lung functions and correlations with microvascular leakage and lung edema in allergen-challenged Brown Norway rats. Pulm Pharmacol Ther. 2013;26(6):677–684.
   PubMed Web of Science ®Google Scholar
• Gil MA, Caniga M, Woodhouse JD, et al. Anti-inflammatory actions of chemoattractant receptor-homologous molecule expressed on Th2 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
• Wang Y-H, Trucksis M, McElwee JJ, et al. UGT2B17 genetic polymorphisms dramatically affect the pharmacokinetics of MK-7246 in healthy subjects in a first-in-human study. Clin Pharmacol Ther. 2012;92(1):96–102.
   PubMed Web of Science ®Google Scholar
• Ishizuka T, Matsui T, Okamoto Y, et al. Ramatroban (BAY u 3405): a novel dual antagonist of TXA2 receptor and CRTh2, a newly identified prostaglandin D2 receptor. Cardiovasc Drug Rev. 2004;22(2):71–90.
   PubMed Web of Science ®Google Scholar
• Ulven T, Kostenis E. Minor structural modifications convert the dual TP/CRTH2 antagonist ramatroban into a highly selective and potent CRTH2 antagonist. J Med Chem. 2005;48(4):897–900.
   PubMed Web of Science ®Google Scholar
• Liu J, Li A-R, Wang Y, et al. Discovery of AMG 853, a CRTH2 and DP dual antagonist. ACS Med Chem Lett. 2011;2(5):326–330.
   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(2):339–345.
   PubMed Web of Science ®Google Scholar
• Wang Y, Fu Z, Schmitt M, et al. Optimization of phenylacetic acid derivatives for CRTH2 and DP selective antagonism. Bioorg Med Chem Lett. 2012;22(1):367–370.
   PubMed Web of Science ®Google Scholar