IUPHAR/BPS Guide to Pharmacology CITE

NADPH oxidases (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Albert van der Vliet1
  1. University of Vermont, USA


The two DUOX enzymes were originally identified as participating in the production of hydrogen peroxide as a pre-requisite for thyroid hormone biosynthesis in the thyroid gland [6].
NOX enzymes function to catalyse the reduction of molecular oxygen to superoxide and various other reactive oxygen species (ROS). They are subunits of the NADPH oxidase complex.


This is a citation summary for NADPH oxidases in the Guide to Pharmacology database (GtoPdb). It exists purely as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analyzers. Readers will almost certainly want to visit the relevant sections of the database which are given here under database links.

GtoPdb is an expert-driven guide to pharmacological targets and the substances that act on them. GtoPdb is a reference work which is most usefully represented as an on-line database. As in any publication this work should be appropriately cited, and the papers it cites should also be recognized. This document provides a citation for the relevant parts of the database, and also provides a reference list for the research cited by those parts.

Please note that the database version for the citations given in GtoPdb are to the most recent preceding version in which the family or its subfamilies and targets were substantially changed. The links below are to the current version. If you need to consult the cited version, rather than the most recent version, please contact the GtoPdb curators.

Database links

NADPH oxidases
            DUOX1(dual oxidase 1)
            DUOX2(dual oxidase 2)
            NOX1(NADPH oxidase 1)
            NOX2(cytochrome b-245 beta chain)
            NOX3(NADPH oxidase 3)
            NOX4(NADPH oxidase 4)
            NOX5(NADPH oxidase 5)


  1. Aoyama T, Paik YH, Watanabe S, Laleu B, Gaggini F, Fioraso-Cartier L, Molango S, Heitz F, Merlot C and Szyndralewiez C et al.. (2012) Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology 56: 2316-27 [PMID:22806357]
  2. Barman SA, Chen F, Su Y, Dimitropoulou C, Wang Y, Catravas JD, Han W, Orfi L, Szantai-Kis C and Keri G et al.. (2014) NADPH oxidase 4 is expressed in pulmonary artery adventitia and contributes to hypertensive vascular remodeling. Arterioscler. Thromb. Vasc. Biol. 34: 1704-15 [PMID:24947524]
  3. Bánfi B, Maturana A, Jaconi S, Arnaudeau S, Laforge T, Sinha B, Ligeti E, Demaurex N and Krause KH. (2000) A mammalian H+ channel generated through alternative splicing of the NADPH oxidase homolog NOH-1. Science 287: 138-42 [PMID:10615049]
  4. Bánfi B, Molnár G, Maturana A, Steger K, Hegedûs B, Demaurex N and Krause KH. (2001) A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes. J. Biol. Chem. 276: 37594-601 [PMID:11483596]
  5. De Deken X, Corvilain B, Dumont JE and Miot F. (2014) Roles of DUOX-mediated hydrogen peroxide in metabolism, host defense, and signaling. Antioxid. Redox Signal. 20: 2776-93 [PMID:24161126]
  6. De Deken X, Wang D, Many MC, Costagliola S, Libert F, Vassart G, Dumont JE and Miot F. (2000) Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family. J. Biol. Chem. 275: 23227-33 [PMID:10806195]
  7. Donkó A, Ruisanchez E, Orient A, Enyedi B, Kapui R, Péterfi Z, de Deken X, Benyó Z and Geiszt M. (2010) Urothelial cells produce hydrogen peroxide through the activation of Duox1. Free Radic. Biol. Med. 49: 2040-8 [PMID:21146788]
  8. Dupuy C, Ohayon R, Valent A, Noël-Hudson MS, Dème D and Virion A. (1999) Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cdnas. J. Biol. Chem. 274: 37265-9 [PMID:10601291]
  9. El Hassani RA, Benfares N, Caillou B, Talbot M, Sabourin JC, Belotte V, Morand S, Gnidehou S, Agnandji D and Ohayon R et al.. (2005) Dual oxidase2 is expressed all along the digestive tract. Am. J. Physiol. Gastrointest. Liver Physiol. 288: G933-42 [PMID:15591162]
  10. Gaggini F, Laleu B, Orchard M, Fioraso-Cartier L, Cagnon L, Houngninou-Molango S, Gradia A, Duboux G, Merlot C and Heitz F et al.. (2011) Design, synthesis and biological activity of original pyrazolo-pyrido-diazepine, -pyrazine and -oxazine dione derivatives as novel dual Nox4/Nox1 inhibitors. Bioorg. Med. Chem. 19: 6989-99 [PMID:22041175]
  11. Geiszt M, Witta J, Baffi J, Lekstrom K and Leto TL. (2003) Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense. FASEB J. 17: 1502-4 [PMID:12824283]
  12. Ghatak S, Hascall VC, Markwald RR, Feghali-Bostwick C, Artlett CM, Gooz M, Bogatkevich GS, Atanelishvili I, Silver RM and Wood J et al.. (2017) Transforming growth factor β1 (TGFβ1)-induced CD44V6-NOX4 signaling in pathogenesis of idiopathic pulmonary fibrosis. J. Biol. Chem. 292: 10490-10519 [PMID:28389561]
  13. Habibovic A, Hristova M, Heppner DE, Danyal K, Ather JL, Janssen-Heininger YM, Irvin CG, Poynter ME, Lundblad LK and Dixon AE et al.. (2016) DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma. JCI Insight 1: e88811 [PMID:27812543]
  14. Hecker L, Vittal R, Jones T, Jagirdar R, Luckhardt TR, Horowitz JC, Pennathur S, Martinez FJ and Thannickal VJ. (2009) NADPH oxidase-4 mediates myofibroblast activation and fibrogenic responses to lung injury. Nat. Med. 15: 1077-81 [PMID:19701206]
  15. Hirakawa S, Saito R, Ohara H, Okuyama R and Aiba S. (2011) Dual oxidase 1 induced by Th2 cytokines promotes STAT6 phosphorylation via oxidative inactivation of protein tyrosine phosphatase 1B in human epidermal keratinocytes. J. Immunol. 186: 4762-70 [PMID:21411736]
  16. Kuroda J, Ago T, Matsushima S, Zhai P, Schneider MD and Sadoshima J. (2010) NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc. Natl. Acad. Sci. U.S.A. 107: 15565-70 [PMID:20713697]
  17. Kwon J, Shatynski KE, Chen H, Morand S, de Deken X, Miot F, Leto TL and Williams MS. (2010) The nonphagocytic NADPH oxidase Duox1 mediates a positive feedback loop during T cell receptor signaling. Sci Signal 3: ra59 [PMID:20682913]
  18. Laleu B, Gaggini F, Orchard M, Fioraso-Cartier L, Cagnon L, Houngninou-Molango S, Gradia A, Duboux G, Merlot C and Heitz F et al.. (2010) First in class, potent, and orally bioavailable NADPH oxidase isoform 4 (Nox4) inhibitors for the treatment of idiopathic pulmonary fibrosis. J. Med. Chem. 53: 7715-30 [PMID:20942471]
  19. Lu J, Risbood P, Kane Jr CT, Hossain MT, Anderson L, Hill K, Monks A, Wu Y, Antony S and Juhasz A et al.. (2017) Characterization of potent and selective iodonium-class inhibitors of NADPH oxidases. Biochem. Pharmacol. 143: 25-38 [PMID:28709950]
  20. Paravicini TM, Chrissobolis S, Drummond GR and Sobey CG. (2004) Increased NADPH-oxidase activity and Nox4 expression during chronic hypertension is associated with enhanced cerebral vasodilatation to NADPH in vivo. Stroke 35: 584-9 [PMID:14739416]
  21. Rada B, Park JJ, Sil P, Geiszt M and Leto TL. (2014) NLRP3 inflammasome activation and interleukin-1β release in macrophages require calcium but are independent of calcium-activated NADPH oxidases. Inflamm. Res. 63: 821-30 [PMID:25048991]
  22. Sato N, Takasaka N, Yoshida M, Tsubouchi K, Minagawa S, Araya J, Saito N, Fujita Y, Kurita Y and Kobayashi K et al.. (2016) Metformin attenuates lung fibrosis development via NOX4 suppression. Respir. Res. 17: 107 [PMID:27576730]
  23. Shiose A, Kuroda J, Tsuruya K, Hirai M, Hirakata H, Naito S, Hattori M, Sakaki Y and Sumimoto H. (2001) A novel superoxide-producing NAD(P)H oxidase in kidney. J. Biol. Chem. 276: 1417-23 [PMID:11032835]
  24. Sommer F and Bäckhed F. (2015) The gut microbiota engages different signaling pathways to induce Duox2 expression in the ileum and colon epithelium. Mucosal Immunol 8: 372-9 [PMID:25160818]
  25. Sorescu D, Weiss D, Lassègue B, Clempus RE, Szöcs K, Sorescu GP, Valppu L, Quinn MT, Lambeth JD and Vega JD et al.. (2002) Superoxide production and expression of nox family proteins in human atherosclerosis. Circulation 105: 1429-35 [PMID:11914250]
  26. van der Vliet A, Danyal K and Heppner DE. (2018) Dual oxidase: a novel therapeutic target in allergic disease. Br. J. Pharmacol. 175: 1401-1418 [PMID:29405261]
  27. Xu Q, Kulkarni AA, Sajith AM, Hussein D, Brown D, Güner OF, Reddy MD, Watkins EB, Lassègue B and Griendling KK et al.. (2018) Design, synthesis, and biological evaluation of inhibitors of the NADPH oxidase, Nox4. Bioorg. Med. Chem. 26: 989-998 [PMID:29426628]