Literature DB >> 28523115

Discovery of Fevipiprant (NVP-QAW039), a Potent and Selective DP2 Receptor Antagonist for Treatment of Asthma.

David A Sandham1, Lucy Barker1, Lyndon Brown1, Zarin Brown1, David Budd1, Steven J Charlton1, Devnandan Chatterjee1, Brian Cox1, Gerald Dubois1, Nicholas Duggan1, Edward Hall1, Julia Hatto1, Janet Maas1, Jodie Manini1, Rachael Profit1, Darren Riddy1, Catherine Ritchie1, Bindi Sohal1, Duncan Shaw1, Rowan Stringer1, David A Sykes1, Matthew Thomas1, Katharine L Turner1, Simon J Watson1, Ryan West1, Elisabeth Willard1, Gareth Williams1, Jennifer Willis1.   

Abstract

Further optimization of an initial DP2 receptor antagonist clinical candidate NVP-QAV680 led to the discovery of a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acetic acid (compound 11, NVP-QAW039, fevipiprant), which exhibits improved potency on human eosinophils and Th2 cells, together with a longer receptor residence time, and is currently in clinical trials for severe asthma.

Entities:  

Keywords:  DP2 receptor antagonist; clinical candidate; severe asthma

Year:  2017        PMID： 28523115      PMCID： PMC5430394          DOI： 10.1021/acsmedchemlett.7b00157

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  19 in total

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Journal:  Bioorg Med Chem Lett       Date:  2014-10-15       Impact factor: 2.823

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Journal:  Bioorg Med Chem Lett       Date:  2014-08-19       Impact factor: 2.823

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Journal:  Bioorg Med Chem Lett       Date:  2011-09-05       Impact factor: 2.823

4.  Pharmacological characterization of CRTh2 antagonist LAS191859: Long receptor residence time translates into long-lasting in vivo efficacy.

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Journal:  Lancet       Date:  2016-04-27       Impact factor: 79.321

7.  Fevipiprant, a prostaglandin D2 receptor 2 antagonist, in patients with persistent eosinophilic asthma: a single-centre, randomised, double-blind, parallel-group, placebo-controlled trial.

Authors:  Sherif Gonem; Rachid Berair; Amisha Singapuri; Ruth Hartley; Marie F M Laurencin; Gerald Bacher; Björn Holzhauer; Michelle Bourne; Vijay Mistry; Ian D Pavord; Adel H Mansur; Andrew J Wardlaw; Salman H Siddiqui; Richard A Kay; Christopher E Brightling
Journal:  Lancet Respir Med       Date:  2016-08-05       Impact factor: 30.700

8.  The Influence of receptor kinetics on the onset and duration of action and the therapeutic index of NVA237 and tiotropium.

Authors:  David A Sykes; Mark R Dowling; Juliet Leighton-Davies; Toby C Kent; Lindsay Fawcett; Emilie Renard; Alexandre Trifilieff; Steven J Charlton
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9.  Prostaglandin D2 selectively induces chemotaxis in T helper type 2 cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2.

Authors:  H Hirai; K Tanaka; O Yoshie; K Ogawa; K Kenmotsu; Y Takamori; M Ichimasa; K Sugamura; M Nakamura; S Takano; K Nagata
Journal:  J Exp Med       Date:  2001-01-15       Impact factor: 14.307

10.  The Influence of IgE on Cultured Human Mast Cells.

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Journal:  Allergy Asthma Immunol Res       Date:  2013-08-27       Impact factor: 5.764
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Review 4.  The prostaglandin D2 receptor 2 pathway in asthma: a key player in airway inflammation.

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6.  The Roles of Type 2 Cytotoxic T Cells in Inflammation, Tissue Remodeling, and Prostaglandin (PG) D2 Production Are Attenuated by PGD2 Receptor 2 Antagonism.

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Journal:  J Immunol       Date:  2021-05-19       Impact factor: 5.422

7.  Prostaglandin D2 metabolites activate asthmatic patient-derived type 2 innate lymphoid cells and eosinophils via the DP2 receptor.

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Journal:  Respir Res       Date:  2021-10-07

Review 8.  Cyclopentenone Prostaglandins: Biologically Active Lipid Mediators Targeting Inflammation.

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  8 in total

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