Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZPJQCC)

DOT Name NADPH oxidase 1 (NOX1)
Synonyms NOX-1; EC 1.6.3.-; Mitogenic oxidase 1; MOX-1; NADH/NADPH mitogenic oxidase subunit P65-MOX; NOH-1
Gene Name NOX1
Related Disease
Adenocarcinoma ( )
Advanced cancer ( )
Arteriosclerosis ( )
Atherosclerosis ( )
Bladder cancer ( )
Breast neoplasm ( )
Carcinoma ( )
Cardiac failure ( )
Chronic granulomatous disease ( )
Colitis ( )
Colon cancer ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Congestive heart failure ( )
Gastritis ( )
Glioma ( )
Granulomatous disease, chronic, X-linked ( )
Hepatocellular carcinoma ( )
Inflammatory bowel disease ( )
Leukemia ( )
Liver cirrhosis ( )
Major depressive disorder ( )
Metabolic disorder ( )
Nephropathy ( )
Nervous system disease ( )
Non-alcoholic fatty liver disease ( )
Osteoporosis ( )
Parkinson disease ( )
Prostate cancer ( )
Prostate carcinoma ( )
Prostate neoplasm ( )
Pulmonary arterial hypertension ( )
Type-1/2 diabetes ( )
Ulcerative colitis ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Cardiovascular disease ( )
Chronic pancreatitis ( )
Colon carcinoma ( )
Diabetic kidney disease ( )
Gastric cancer ( )
Nasopharyngeal carcinoma ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Adult glioblastoma ( )
Amyotrophic lateral sclerosis ( )
Glioblastoma multiforme ( )
Lung adenocarcinoma ( )
Obesity ( )
UniProt ID
NOX1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
EC Number
1.6.3.-
Pfam ID
PF08022 ; PF01794 ; PF08030
Sequence
MGNWVVNHWFSVLFLVVWLGLNVFLFVDAFLKYEKADKYYYTRKILGSTLACARASALCL
NFNSTLILLPVCRNLLSFLRGTCSFCSRTLRKQLDHNLTFHKLVAYMICLHTAIHIIAHL
FNFDCYSRSRQATDGSLASILSSLSHDEKKGGSWLNPIQSRNTTVEYVTFTSIAGLTGVI
MTIALILMVTSATEFIRRSYFEVFWYTHHLFIFYILGLGIHGIGGIVRGQTEESMNESHP
RKCAESFEMWDDRDSHCRRPKFEGHPPESWKWILAPVILYICERILRFYRSQQKVVITKV
VMHPSKVLELQMNKRGFSMEVGQYIFVNCPSISLLEWHPFTLTSAPEEDFFSIHIRAAGD
WTENLIRAFEQQYSPIPRIEVDGPFGTASEDVFQYEVAVLVGAGIGVTPFASILKSIWYK
FQCADHNLKTKKIYFYWICRETGAFSWFNNLLTSLEQEMEELGKVGFLNYRLFLTGWDSN
IVGHAALNFDKATDIVTGLKQKTSFGRPMWDNEFSTIATSHPKSVVGVFLCGPRTLAKSL
RKCCHRYSSLDPRKVQFYFNKENF
Function
NADPH oxidase that catalyzes the generation of superoxide from molecular oxygen utilizing NADPH as an electron donor; [Isoform NOH-1L]: NADPH oxidase that catalyzes the generation of superoxide from molecular oxygen utilizing NADPH as an electron donor; [Isoform NOH-1S]: Voltage-gated proton channel that mediates the H(+) currents of resting phagocytes and other tissues. It participates in the regulation of cellular pH and is blocked by zinc.
Tissue Specificity .Detected in colon, uterus, prostate, and colon carcinoma, but not in peripheral blood leukocytes.; [Isoform NOH-1S]: Detected only in colon and colon carcinoma cells.
KEGG Pathway
Osteoclast differentiation (hsa04380 )
AGE-RAGE sig.ling pathway in diabetic complications (hsa04933 )
Alzheimer disease (hsa05010 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Lipid and atherosclerosis (hsa05417 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
RAC1 GTPase cycle (R-HSA-9013149 )
RAC3 GTPase cycle (R-HSA-9013423 )
WNT5 (R-HSA-9673324 )
RHO GTPases Activate NADPH Oxidases (R-HSA-5668599 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adenocarcinoma DIS3IHTY Strong Altered Expression [1]
Advanced cancer DISAT1Z9 Strong Altered Expression [2]
Arteriosclerosis DISK5QGC Strong Biomarker [3]
Atherosclerosis DISMN9J3 Strong Biomarker [3]
Bladder cancer DISUHNM0 Strong Biomarker [4]
Breast neoplasm DISNGJLM Strong Biomarker [5]
Carcinoma DISH9F1N Strong Biomarker [6]
Cardiac failure DISDC067 Strong Biomarker [7]
Chronic granulomatous disease DIS9ZR24 Strong Genetic Variation [8]
Colitis DISAF7DD Strong Biomarker [9]
Colon cancer DISVC52G Strong Biomarker [10]
Colonic neoplasm DISSZ04P Strong Biomarker [11]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [12]
Congestive heart failure DIS32MEA Strong Biomarker [7]
Gastritis DIS8G07K Strong Altered Expression [13]
Glioma DIS5RPEH Strong Biomarker [14]
Granulomatous disease, chronic, X-linked DISNTTS3 Strong Genetic Variation [15]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [16]
Inflammatory bowel disease DISGN23E Strong Biomarker [9]
Leukemia DISNAKFL Strong Biomarker [17]
Liver cirrhosis DIS4G1GX Strong Altered Expression [18]
Major depressive disorder DIS4CL3X Strong Biomarker [19]
Metabolic disorder DIS71G5H Strong Biomarker [20]
Nephropathy DISXWP4P Strong Altered Expression [2]
Nervous system disease DISJ7GGT Strong Biomarker [19]
Non-alcoholic fatty liver disease DISDG1NL Strong Biomarker [21]
Osteoporosis DISF2JE0 Strong Biomarker [22]
Parkinson disease DISQVHKL Strong Altered Expression [23]
Prostate cancer DISF190Y Strong Genetic Variation [24]
Prostate carcinoma DISMJPLE Strong Genetic Variation [24]
Prostate neoplasm DISHDKGQ Strong Biomarker [25]
Pulmonary arterial hypertension DISP8ZX5 Strong Biomarker [26]
Type-1/2 diabetes DISIUHAP Strong Biomarker [27]
Ulcerative colitis DIS8K27O Strong Genetic Variation [28]
Urinary bladder cancer DISDV4T7 Strong Biomarker [4]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [4]
Cardiovascular disease DIS2IQDX moderate Biomarker [29]
Chronic pancreatitis DISBUOMJ moderate Biomarker [30]
Colon carcinoma DISJYKUO moderate Biomarker [10]
Diabetic kidney disease DISJMWEY moderate Biomarker [31]
Gastric cancer DISXGOUK moderate Biomarker [32]
Nasopharyngeal carcinoma DISAOTQ0 moderate Altered Expression [33]
Squamous cell carcinoma DISQVIFL moderate Biomarker [34]
Stomach cancer DISKIJSX moderate Biomarker [32]
Adult glioblastoma DISVP4LU Limited Biomarker [24]
Amyotrophic lateral sclerosis DISF7HVM Limited Genetic Variation [35]
Glioblastoma multiforme DISK8246 Limited Biomarker [24]
Lung adenocarcinoma DISD51WR Limited Altered Expression [1]
Obesity DIS47Y1K Limited Biomarker [36]
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⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Arsenic DMTL2Y1 Approved Arsenic increases the expression of NADPH oxidase 1 (NOX1). [37]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of NADPH oxidase 1 (NOX1). [38]
Testosterone DM7HUNW Approved Testosterone increases the expression of NADPH oxidase 1 (NOX1). [38]
Niclosamide DMJAGXQ Approved Niclosamide decreases the expression of NADPH oxidase 1 (NOX1). [39]
Dalcetrapib DMKNCVM Phase 3 Dalcetrapib increases the expression of NADPH oxidase 1 (NOX1). [40]
Anacetrapib DMP2BFG Phase 3 Anacetrapib increases the expression of NADPH oxidase 1 (NOX1). [40]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 decreases the expression of NADPH oxidase 1 (NOX1). [41]
Torcetrapib DMDHYM7 Discontinued in Phase 2 Torcetrapib increases the expression of NADPH oxidase 1 (NOX1). [40]
Acteoside DM0YHKB Terminated Acteoside decreases the activity of NADPH oxidase 1 (NOX1). [42]
Nickel chloride DMI12Y8 Investigative Nickel chloride increases the expression of NADPH oxidase 1 (NOX1). [43]
Hexadecanoic acid DMWUXDZ Investigative Hexadecanoic acid increases the expression of NADPH oxidase 1 (NOX1). [44]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE DMNQL17 Investigative 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the expression of NADPH oxidase 1 (NOX1). [45]
U0126 DM31OGF Investigative U0126 decreases the expression of NADPH oxidase 1 (NOX1). [45]
BAY11-7082 DMQNOFA Investigative BAY11-7082 decreases the expression of NADPH oxidase 1 (NOX1). [46]
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⏷ Show the Full List of 14 Drug(s)
1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT
Drug Name Drug ID Highest Status Interaction REF
carvacrol DMINM2D Investigative carvacrol affects the binding of NADPH oxidase 1 (NOX1). [47]
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References

1 HIF-1 alpha signaling is augmented during intermittent hypoxia by induction of the Nrf2 pathway in NOX1-expressing adenocarcinoma A549 cells.Free Radic Biol Med. 2010 Jun 15;48(12):1626-35. doi: 10.1016/j.freeradbiomed.2010.03.008. Epub 2010 Mar 24.
2 Nox1 downregulators: A new class of therapeutics.Steroids. 2019 Dec;152:108494. doi: 10.1016/j.steroids.2019.108494. Epub 2019 Sep 10.
3 Reactive Oxygen Species Can Provide Atheroprotection via NOX4-Dependent Inhibition of Inflammation and Vascular Remodeling.Arterioscler Thromb Vasc Biol. 2016 Feb;36(2):295-307. doi: 10.1161/ATVBAHA.115.307012. Epub 2015 Dec 29.
4 A novel human AlkB homologue, ALKBH8, contributes to human bladder cancer progression.Cancer Res. 2009 Apr 1;69(7):3157-64. doi: 10.1158/0008-5472.CAN-08-3530. Epub 2009 Mar 17.
5 Oxidative stress specifically downregulates survivin to promote breast tumour formation.Br J Cancer. 2013 Mar 5;108(4):848-58. doi: 10.1038/bjc.2013.40. Epub 2013 Feb 12.
6 NADPH oxidases and cancer.Clin Sci (Lond). 2015 Jun;128(12):863-75. doi: 10.1042/CS20140542.
7 MnSOD protects against COX1-mediated endothelial dysfunction in chronic heart failure.Am J Physiol Heart Circ Physiol. 2010 May;298(5):H1600-7. doi: 10.1152/ajpheart.01108.2009. Epub 2010 Mar 19.
8 Colitis susceptibility in mice with reactive oxygen species deficiency is mediated by mucus barrier and immune defense defects.Mucosal Immunol. 2019 Nov;12(6):1316-1326. doi: 10.1038/s41385-019-0205-x. Epub 2019 Sep 25.
9 NOX1-derived ROS drive the expression of Lipocalin-2 in colonic epithelial cells in inflammatory conditions.Mucosal Immunol. 2019 Jan;12(1):117-131. doi: 10.1038/s41385-018-0086-4. Epub 2018 Oct 2.
10 NOX1-Dependent mTORC1 Activation via S100A9 Oxidation in Cancer Stem-like Cells Leads to Colon Cancer Progression.Cell Rep. 2019 Jul 30;28(5):1282-1295.e8. doi: 10.1016/j.celrep.2019.06.085.
11 NADPH oxidase overexpression in human colon cancers and rat colon tumors induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).Int J Cancer. 2011 Jun 1;128(11):2581-90. doi: 10.1002/ijc.25610. Epub 2010 Oct 8.
12 Subverted regulation of Nox1 NADPH oxidase-dependent oxidant generation by protein disulfide isomerase A1 in colon carcinoma cells with overactivated KRas.Cell Death Dis. 2019 Feb 13;10(2):143. doi: 10.1038/s41419-019-1402-y.
13 NF-B-induced NOX1 activation promotes gastric tumorigenesis through the expansion of SOX2-positive epithelial cells.Oncogene. 2019 May;38(22):4250-4263. doi: 10.1038/s41388-019-0702-0. Epub 2019 Jan 30.
14 A novel interaction of PAK4 with PPAR to regulate Nox1 and radiation-induced epithelial-to-mesenchymal transition in glioma.Oncogene. 2017 Sep 14;36(37):5309-5320. doi: 10.1038/onc.2016.261. Epub 2017 May 22.
15 NOX4 is the main NADPH oxidase involved in the early stages of hematopoietic differentiation from human induced pluripotent stem cells.Free Radic Biol Med. 2020 Jan;146:107-118. doi: 10.1016/j.freeradbiomed.2019.10.005. Epub 2019 Oct 15.
16 SHMT1 inhibits the metastasis of HCC by repressing NOX1-mediated ROS production.J Exp Clin Cancer Res. 2019 Feb 12;38(1):70. doi: 10.1186/s13046-019-1067-5.
17 NAD(P)H oxidase 1, a product of differentiated colon epithelial cells, can partially replace glycoprotein 91phox in the regulated production of superoxide by phagocytes.J Immunol. 2003 Jul 1;171(1):299-306. doi: 10.4049/jimmunol.171.1.299.
18 Deficiency of NOX1 or NOX4 Prevents Liver Inflammation and Fibrosis in Mice through Inhibition of Hepatic Stellate Cell Activation.PLoS One. 2015 Jul 29;10(7):e0129743. doi: 10.1371/journal.pone.0129743. eCollection 2015.
19 Depressive-Like Behaviors Are Regulated by NOX1/NADPH Oxidase by Redox Modification of NMDA Receptor 1.J Neurosci. 2017 Apr 12;37(15):4200-4212. doi: 10.1523/JNEUROSCI.2988-16.2017. Epub 2017 Mar 17.
20 Genetic Deletion of NADPH Oxidase 1 Rescues Microvascular Function in Mice With Metabolic Disease.Circ Res. 2017 Aug 18;121(5):502-511. doi: 10.1161/CIRCRESAHA.116.309965. Epub 2017 Jul 6.
21 The NOX1 isoform of NADPH oxidase is involved in dysfunction of liver sinusoids in nonalcoholic fatty liver disease.Free Radic Biol Med. 2018 Feb 1;115:412-420. doi: 10.1016/j.freeradbiomed.2017.12.019. Epub 2017 Dec 20.
22 Pharmacokinetic Study of NADPH Oxidase Inhibitor Ewha-18278, a Pyrazole Derivative.Pharmaceutics. 2019 Sep 17;11(9):482. doi: 10.3390/pharmaceutics11090482.
23 Dysregulation of serum NADPH oxidase1 and ferritin levels provides insights into diagnosis of Parkinson's disease.Clin Biochem. 2017 Dec;50(18):1087-1092. doi: 10.1016/j.clinbiochem.2017.09.014. Epub 2017 Sep 20.
24 NADPH Oxidases NOXs and DUOXs as putative targets for cancer therapy.Anticancer Agents Med Chem. 2013 Mar;13(3):502-14.
25 Increased Nox1 and hydrogen peroxide in prostate cancer.Prostate. 2005 Feb 1;62(2):200-7. doi: 10.1002/pros.20137.
26 Serotonin Signaling Through the 5-HT(1B) Receptor and NADPH Oxidase 1 in Pulmonary Arterial Hypertension.Arterioscler Thromb Vasc Biol. 2017 Jul;37(7):1361-1370. doi: 10.1161/ATVBAHA.116.308929. Epub 2017 May 4.
27 Relationship of NADPH Oxidase-1 expression to beta cell dysfunction induced by inflammatory cytokines.Biochem Biophys Res Commun. 2017 Apr 1;485(2):290-294. doi: 10.1016/j.bbrc.2017.02.089. Epub 2017 Feb 21.
28 NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.Mucosal Immunol. 2018 Mar;11(2):562-574. doi: 10.1038/mi.2017.74. Epub 2017 Nov 1.
29 GPER blockers as Nox downregulators: A new drug class to target chronic non-communicable diseases.J Steroid Biochem Mol Biol. 2018 Feb;176:82-87. doi: 10.1016/j.jsbmb.2017.03.019. Epub 2017 Mar 23.
30 NADPH oxidase 1 mediates caerulein-induced pancreatic fibrosis in chronic pancreatitis.Free Radic Biol Med. 2020 Feb 1;147:139-149. doi: 10.1016/j.freeradbiomed.2019.11.034. Epub 2019 Dec 16.
31 APX-115, a first-in-class pan-NADPH oxidase (Nox) inhibitor, protects db/db mice from renal injury.Lab Invest. 2017 Apr;97(4):419-431. doi: 10.1038/labinvest.2017.2. Epub 2017 Feb 6.
32 Identification and Characterization of a Novel NADPH Oxidase 1 (Nox1) Inhibitor That Suppresses Proliferation of Colon and Stomach Cancer Cells.Biol Pharm Bull. 2018 Mar 1;41(3):419-426. doi: 10.1248/bpb.b17-00804. Epub 2017 Dec 22.
33 Changes in the nasopharyngeal carcinoma nuclear proteome induced by the EBNA1 protein of Epstein-Barr virus reveal potential roles for EBNA1 in metastasis and oxidative stress responses.J Virol. 2012 Jan;86(1):382-94. doi: 10.1128/JVI.05648-11. Epub 2011 Oct 19.
34 Inhibition of Nox1 induces apoptosis by attenuating the AKT signaling pathway in oral squamous cell carcinoma cell lines.Oncol Rep. 2016 Nov;36(5):2991-2998. doi: 10.3892/or.2016.5068. Epub 2016 Sep 5.
35 Evaluation of NADPH oxidases as drug targets in a mouse model of familial amyotrophic lateral sclerosis.Free Radic Biol Med. 2016 Aug;97:95-108. doi: 10.1016/j.freeradbiomed.2016.05.016. Epub 2016 May 19.
36 Differential contribution of Nox1, Nox2 and Nox4 to kidney vascular oxidative stress and endothelial dysfunction in obesity.Redox Biol. 2020 Jan;28:101330. doi: 10.1016/j.redox.2019.101330. Epub 2019 Sep 20.
37 Arsenic and chromium in drinking water promote tumorigenesis in a mouse colitis-associated colorectal cancer model and the potential mechanism is ROS-mediated Wnt/-catenin signaling pathway. Toxicol Appl Pharmacol. 2012 Jul 1;262(1):11-21. doi: 10.1016/j.taap.2012.04.014. Epub 2012 Apr 19.
38 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
39 Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
40 Cholesteryl ester-transfer protein inhibitors stimulate aldosterone biosynthesis in adipocytes through Nox-dependent processes. J Pharmacol Exp Ther. 2015 Apr;353(1):27-34.
41 CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
42 The inhibitory effect of phenylpropanoid glycosides and iridoid glucosides on free radical production and beta2 integrin expression in human leucocytes. J Pharm Pharmacol. 2006 Jan;58(1):129-35. doi: 10.1211/jpp.58.1.0016.
43 Nickel-induced epithelial-mesenchymal transition by reactive oxygen species generation and E-cadherin promoter hypermethylation. J Biol Chem. 2012 Jul 20;287(30):25292-302.
44 Geraniol improves endothelial function by inhibiting NOX-2 derived oxidative stress in high fat diet fed mice. Biochem Biophys Res Commun. 2016 May 20;474(1):182-187. doi: 10.1016/j.bbrc.2016.04.097. Epub 2016 Apr 21.
45 Intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. Carcinogenesis. 2012 Apr;33(4):876-85. doi: 10.1093/carcin/bgs097. Epub 2012 Feb 3.
46 Caveolin-1 is a negative regulator of NADPH oxidase-derived reactive oxygen species. Free Radic Biol Med. 2014 Aug;73:201-13. doi: 10.1016/j.freeradbiomed.2014.04.029. Epub 2014 May 14.
47 In vivo and In silico evidence of the protective properties of carvacrol against experimentally-induced gastric ulcer: Implication of antioxidant, anti-inflammatory, and antiapoptotic mechanisms. Chem Biol Interact. 2023 Sep 1;382:110649. doi: 10.1016/j.cbi.2023.110649. Epub 2023 Jul 25.