Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQDX9RY)

• DOT Name: NADPH oxidase activator 1 (NOXA1)
• Synonyms: NOX activator 1; Antigen NY-CO-31; NCF2-like protein; P67phox-like factor; p51-nox
• Gene Name: NOXA1
• Related Disease:
  Advanced cancer
  Arteriosclerosis
  Atherosclerosis
  Vascular disease
  Adenocarcinoma
• UniProt ID: NOXA1_HUMAN
• PDB ID: 7CFZ
• Pfam ID: PF00564 ; PF00018
• Sequence:
  MASLGDLVRAWHLGAQAVDRGDWARALHLFSGVPAPPARLCFNAGCVHLLAGDPEAALRA
  FDQAVTKDTCMAVGFFQRGVANFQLARFQEALSDFWLALEQLRGHAAIDYTQLGLRFKLQ
  AWEVLHNVASAQCQLGLWTEAASSLREAMSKWPEGSLNGLDSALDQVQRRGSLPPRQVPR
  GEVFRPHRWHLKHLEPVDFLGKAKVVASAIPDDQGWGVRPQQPQGPGANHDARSLIMDSP
  RAGTHQGPLDAETEVGADRCTSTAYQEQRPQVEQVGKQAPLSPGLPAMGGPGPGPCEDPA
  GAGGAGAGGSEPLVTVTVQCAFTVALRARRGADLSSLRALLGQALPHQAQLGQLSYLAPG
  EDGHWVPIPEEESLQRAWQDAAACPRGLQLQCRGAGGRPVLYQVVAQHSYSAQGPEDLGF
  RQGDTVDVLCEVDQAWLEGHCDGRIGIFPKCFVVPAGPRMSGAPGRLPRSQQGDQP
• Function: Functions as an activator of NOX1, a superoxide-producing NADPH oxidase. Functions in the production of reactive oxygen species (ROS) which participate in a variety of biological processes including host defense, hormone biosynthesis, oxygen sensing and signal transduction. May also activate CYBB/gp91phox and NOX3.
• Tissue Specificity: Widely expressed. Detected in pancreas, liver, kidney, spleen, prostate, small intestine and colon.
• 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

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[2]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[2]
Vascular disease	DISVS67S	Strong	Altered Expression	[3]
Adenocarcinoma	DIS3IHTY	moderate	Biomarker	[4]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of NADPH oxidase activator 1 (NOXA1).	[5]

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of NADPH oxidase activator 1 (NOXA1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of NADPH oxidase activator 1 (NOXA1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of NADPH oxidase activator 1 (NOXA1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of NADPH oxidase activator 1 (NOXA1).	[9]

References

• [1] Expression of NADPH oxidase homologues and accessory genes in human cancer cell lines, tumours and adjacent normal tissues.Free Radic Res. 2009 Jun;43(6):523-32. doi: 10.1080/10715760902918683.
• [2] NOXA1-dependent NADPH oxidase regulates redox signaling and phenotype of vascular smooth muscle cell during atherogenesis.Redox Biol. 2019 Feb;21:101063. doi: 10.1016/j.redox.2018.11.021. Epub 2018 Nov 29.
• [3] Nox activator 1: a potential target for modulation of vascular reactive oxygen species in atherosclerotic arteries.Circulation. 2010 Feb 2;121(4):549-59. doi: 10.1161/CIRCULATIONAHA.109.908319. Epub 2010 Jan 18.
• [4] Evidence for cancer-associated expression of NADPH oxidase 1 (Nox1)-based oxidase system in the human stomach.Free Radic Biol Med. 2007 Dec 15;43(12):1627-38. doi: 10.1016/j.freeradbiomed.2007.08.029. Epub 2007 Sep 14.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [7] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [8] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [9] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.