Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQRBSJ)

• DTT Name: NADPH oxidase 4 (NOX4)
• Synonyms: Renal NAD(P)Hoxidase; Renal NAD(P)H-oxidase; RENOX; Kidney superoxideproducing NADPH oxidase; Kidney superoxide-producing NADPH oxidase; Kidney oxidase1; Kidney oxidase-1; KOX1; KOX-1
• Gene Name: NOX4
• DTT Type: Clinical trial target; [1]
• BioChemical Class: NADH/NADPH oxidoreductase
• UniProt ID: NOX4_HUMAN
• TTD ID: T29741
• EC Number: EC 1.6.3.-
• Sequence:
  MAVSWRSWLANEGVKHLCLFIWLSMNVLLFWKTFLLYNQGPEYHYLHQMLGLGLCLSRAS
  ASVLNLNCSLILLPMCRTLLAYLRGSQKVPSRRTRRLLDKSRTFHITCGVTICIFSGVHV
  AAHLVNALNFSVNYSEDFVELNAARYRDEDPRKLLFTTVPGLTGVCMVVVLFLMITASTY
  AIRVSNYDIFWYTHNLFFVFYMLLTLHVSGGLLKYQTNLDTHPPGCISLNRTSSQNISLP
  EYFSEHFHEPFPEGFSKPAEFTQHKFVKICMEEPRFQANFPQTWLWISGPLCLYCAERLY
  RYIRSNKPVTIISVMSHPSDVMEIRMVKENFKARPGQYITLHCPSVSALENHPFTLTMCP
  TETKATFGVHLKIVGDWTERFRDLLLPPSSQDSEILPFIQSRNYPKLYIDGPFGSPFEES
  LNYEVSLCVAGGIGVTPFASILNTLLDDWKPYKLRRLYFIWVCRDIQSFRWFADLLCMLH
  NKFWQENRPDYVNIQLYLSQTDGIQKIIGEKYHALNSRLFIGRPRWKLLFDEIAKYNRGK
  TVGVFCCGPNSLSKTLHKLSNQNNSYGTRFEYNKESFS
• Function: Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity. Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox.
• KEGG Pathway:
  AGE-RAGE signaling pathway in diabetic complications (hsa04933)
  Alcoholic liver disease (hsa04936)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
• Reactome Pathway:
  STAT5 activation downstream of FLT3 ITD mutants (R-HSA-9702518)
  Signaling by FLT3 fusion proteins (R-HSA-9703465)
  Detoxification of Reactive Oxygen Species (R-HSA-3299685)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
GKT-137831	DMOVB3Y	Fibrosis	GA14-GC01	Phase 2	[1]

References

• [1] Nicotinamide Adenine Dinucleotide Phosphate Oxidase (NOX) in Experimental Liver Fibrosis: GKT137831 as a Novel Potential Therapeutic Agent. Hepatology. 2012 December; 56(6): 2316-2327.