TY - JOUR T1 - Characterization QAW039 and QAV680, two novel, potent and selective CRTh2 antagonists JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P4072 AU - Liz Willard AU - Zarin Brown AU - Charles Owen AU - Gerald Dubois Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P4072.abstract N2 - IntroductionQAW039 is an oral, selective, competitive and reversible CRTh2 receptor antagonist. The present study aims to provide a detailed pharmacological characterisation of QAW039 and QAV680 (two potent and selective CRTh2 antagonists).MethodsAntagonist properties such as potency, selectivity and functional activity of QAW039 and QAV680 were characterized through various pharmacology assays [radio ligand binding, cAMP functional assay, eosinophil shape change (ESC) and Th2 cytokine production].ResultsQAW039 and QAV680 are sub-nM antagonists at the human CRTh2 receptor with an affinity (Ki) of 4.7 and 29 nM respectively. Both compounds are highly selective for CRTh2 receptors, potent inhibitors of ESC, and effectively found to inhibit PGD2- induced IL-3 and IL-5 production from human peripheral blood Th2 cells (Table).View this table:ConclusionQAW039 showed superior potency compared to QAV680 with minimal drop off in whole blood eosinophil shape change assay compared to QAV680 (1.9 vs 15-fold). The efficacy of QAW039 is currently being evaluated clinically in moderate-to-severe asthma patients. ER -