RV568, a narrow-spectrum kinase inhibitor with p38 MAPK-α and -γ selectivity, suppresses COPD inflammation.

The European Respiratory Journal
Catherine E CharronDave Singh

Abstract

Novel anti-inflammatory approaches targeting chronically activated kinase pathways in chronic obstructive pulmonary disease (COPD) are needed. We evaluated RV568, a p38 mitogen-activated protein kinase-α and -γ and SRC family kinase inhibitor, in cellular and in vivo models relevant to COPD and examined its safety and efficacy in COPD patients.The anti-inflammatory activities of RV568 were tested in primary cultured monocytes, macrophages and bronchial epithelial cells and in vivo in lipopolysaccharide and cigarette smoke-exposed murine models. RV568 was evaluated in a 14-day trial in COPD patients.RV568 showed potent anti-inflammatory effects in monocytes and macrophages, which were often greater than those of corticosteroids or the p38 inhibitor Birb796. RV568 combined with corticosteroid had anti-inflammatory effects suggestive of a synergistic interaction in poly I:C-stimulated BEAS-2B cells and in the cigarette smoke model. In COPD patients, inhaled RV568 (50 µg and 100 µg) improved pre-bronchodilator forced expiratory volume in 1 s (69 mL and 48 mL respectively) and significantly reduced sputum malondialdehyde (p<0.05) compared to placebo, although there were no changes in sputum cell counts. Adverse events during RV568 a...Continue Reading

References

Dec 18, 2001·Nature Immunology·Simona SaccaniGioacchino Natoli
Oct 26, 2007·The European Respiratory Journal·T RendaM Saetta
Dec 7, 2007·The Journal of Pharmacology and Experimental Therapeutics·Satyanarayana MedicherlaLinda S Higgins
Aug 23, 2008·Chest·Satoru YanagisawaMasakazu Ichinose
Mar 13, 2010·American Journal of Respiratory and Critical Care Medicine·Yasuo ToPeter J Barnes
Oct 25, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Maria J SmolinskaNicole J Horwood
Nov 18, 2011·Journal of Clinical Pharmacology·David A LomasUNKNOWN Losmapimod Study Investigators
Oct 13, 2012·The European Respiratory Journal·Kate GaffeyDave Singh
Apr 25, 2013·Thorax·Dave Singh
Jul 10, 2013·Respirology : Official Journal of the Asian Pacific Society of Respirology·Balazs AntusImre Barta
Oct 12, 2013·American Journal of Respiratory Cell and Molecular Biology·Patrick GeraghtyRobert F Foronjy
Aug 21, 2015·Respiratory Research·Andrew HighamDave Singh
Jul 5, 2016·The Journal of Allergy and Clinical Immunology·Peter J Barnes

❮ Previous
Next ❯

Citations

Oct 28, 2017·The European Respiratory Journal·Henrik Watz
Apr 5, 2019·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yuki NishimotoYasuo Kizawa
Feb 23, 2020·Expert Review of Respiratory Medicine·Corrado PelaiaGirolamo Pelaia
Sep 15, 2020·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Genki KimuraYasuo Kizawa
Jun 14, 2019·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yuki NishimotoYasuo Kizawa
Jan 25, 2020·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Simon LeaDave Singh
Oct 21, 2020·Nature Reviews. Drug Discovery·Ali A ZarrinDomagoj Vucic
Nov 5, 2020·Fundamental & Clinical Pharmacology·Andrew Higham, Dave Singh
Nov 12, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jennifer M K NguyenVenkataramana K Sidhaye
Sep 4, 2020·Expert Opinion on Emerging Drugs·Federica Lo BelloGaetano Caramori
Apr 2, 2021·Drug Design, Development and Therapy·Corrado PelaiaGirolamo Pelaia
Dec 18, 2020·Current Opinion in Pharmacology·Maria Gabriella MateraClive Page
May 8, 2021·Expert Review of Clinical Pharmacology·Maria Gabriella MateraMario Cazzola
Nov 14, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Haoyang ZhouMark W Feinberg
Aug 7, 2021·International Journal of Chronic Obstructive Pulmonary Disease·Jonathan R Baker, Louise E Donnelly

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here