Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMPX1J9)

• Drug Name: 4-oxo-nonenal Drug Info
• Synonyms: 4-oxo-2E-nonenal

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 6445537
  ChEBI ID: CHEMBL1086447
  CAS Number: CAS 103560-62-9
  TTD Drug ID: DMPX1J9
  INTEDE Drug ID: DR0016

Molecule-Related Drug Atlas

Drug(s) Targeting Transformation-sensitive protein p120 (TRPA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Menthol	DMG2KW7	Back pain	ME84.Z	Approved	[5]
LY3526318	DMFXNQM	Chronic low-back pain	MG30	Phase 2	[6]
HX-100	DMFRM15	Diabetic neuropathy	8C0Z	Phase 1	[7]
NPPB	DMFIWAN	Discovery agent	N.A.	Investigative	[8]
acetaldehyde	DMJFKG4	Discovery agent	N.A.	Investigative	[9]
[3H]resolvin D1	DMFT0HU	Discovery agent	N.A.	Investigative	[10]
Formaldehyde	DM7Q6M0	Discovery agent	N.A.	Investigative	[11]
icilin	DMYVOL9	Discovery agent	N.A.	Investigative	[12]
dibutyl phthalate	DMEDGKO	Discovery agent	N.A.	Investigative	[13]
prostaglandin A2	DMWC4X8	Discovery agent	N.A.	Investigative	[14]

Drug(s) Metabolized By Aldo-keto reductase 1C3 (AKR1C3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxorubicin	DMVP5YE	Acute myelogenous leukaemia	2A41	Approved	[15]
FENOFIBRIC ACID	DMGO2MC	Cardiovascular disease	BA00-BE2Z	Approved	[16]
ANDROSTERONE	DMITJAK	N. A.	N. A.	Phase 3	[17]
Trastuzumab emtansine	DMU1LXS	HER2-positive breast cancer	2C60-2C65	Phase 2	[18]
Acenaphthenol	DMT3QYZ	N. A.	N. A.	Investigative	[17]
Indan-1-ol	DMMLQZJ	N. A.	N. A.	Investigative	[17]

Drug(s) Affected By Aldo-keto reductase family 1 member B10 (AKR1B10)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[19]
Clavulanate	DM2FGRT	Bacteremia	1A73	Approved	[20]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[21]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[22]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[23]
Isoniazid	DM5JVS3	Latent tuberculosis infection		Approved	[24]
Hydroquinone	DM6AVR4	Melasma	ED60.1	Approved	[25]
Reserpine	DM6VM38	Hypertension	BA00-BA04	Approved	[26]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[27]
Disulfiram	DMCL2OK	Alcohol dependence	6C40.2	Approved	[28]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Transformation-sensitive protein p120 (TRPA1)	TTELV3W	TRPA1_HUMAN	Activator	[2]

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Aldo-keto reductase 1C3 (AKR1C3) Main DME	DEGQTXO	AK1C3_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Gene/Protein Processing	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6283).
• [2] Transient receptor potential A1 is a sensory receptor for multiple products of oxidative stress. J Neurosci. 2008 Mar 5;28(10):2485-94.
• [3] Instability of C154Y variant of aldo-keto reductase 1C3. Chem Biol Interact. 2017 Oct 1;276:194-202.
• [4] Role of human aldo-keto-reductase AKR1B10 in the protection against toxic aldehydes. Chem Biol Interact. 2009 Mar 16;178(1-3):145-50.
• [5] TRPV1-mediated itch in seasonal allergic rhinitis. Allergy. 2009 May;64(5):807-10.
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2023. Adis Insight
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] NPPB structure-specifically activates TRPA1 channels. Biochem Pharmacol. 2010 Jul 1;80(1):113-21.
• [9] Transient receptor potential A1 mediates acetaldehyde-evoked pain sensation. Eur J Neurosci. 2007 Nov;26(9):2516-23.
• [10] Resolvin D1 attenuates activation of sensory transient receptor potential channels leading to multiple anti-nociception. Br J Pharmacol. 2010 Oct;161(3):707-20.
• [11] An ion channel essential for sensing chemical damage. J Neurosci. 2007 Oct 17;27(42):11412-5.
• [12] ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell. 2003 Mar 21;112(6):819-29.
• [13] TRPA1 and TRPV1 activation is a novel adjuvant effect mechanism in contact hypersensitivity. J Neuroimmunol. 2009 Feb 15;207(1-2):66-74.
• [14] Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):12045-50.
• [15] Inactivation of the anticancer drugs doxorubicin and oracin by aldo-keto reductase (AKR) 1C3. Toxicol Lett. 2008 Sep;181(1):1-6.
• [16] In vitro metabolism of fenofibric acid by carbonyl reducing enzymes. Chem Biol Interact. 2016 Oct 25;258:153-8.
• [17] Expression and characterization of four recombinant human dihydrodiol dehydrogenase isoforms: oxidation of trans-7, 8-dihydroxy-7,8-dihydrobenzo[a]pyrene to the activated o-quinone metabolite benzo[a]pyrene-7,8-dione. Biochemistry. 1998 May 12;37(19):6781-90.
• [18] The role of carbonyl reducing enzymes in oxcarbazepine in vitro metabolism in man. Chem Biol Interact. 2014 Sep 5;220:241-7.
• [19] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [20] Molecular mechanisms of hepatotoxic cholestasis by clavulanic acid: Role of NRF2 and FXR pathways. Food Chem Toxicol. 2021 Dec;158:112664. doi: 10.1016/j.fct.2021.112664. Epub 2021 Nov 9.
• [21] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [22] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [23] Identification of approved drugs as potent inhibitors of pregnane X receptor activation with differential receptor interaction profiles. Arch Toxicol. 2018 Apr;92(4):1435-1451.
• [24] Characterization of drug-specific signaling between primary human hepatocytes and immune cells. Toxicol Sci. 2017 Jul 1;158(1):76-89.
• [25] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [26] Oxidative stress mechanisms do not discriminate between genotoxic and nongenotoxic liver carcinogens. Chem Res Toxicol. 2015 Aug 17;28(8):1636-46.
• [27] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [28] Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds. Toxicol Sci. 2010 Sep;117(1):81-9.