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

General Information of Drug (ID: DMQ95GE)

• Drug Name: Phenylacetic acid Drug Info
• Synonyms: .alpha.-Toluic acid; .omega.-Phenylacetic acid; 2-Phenylacetic acid; Acetic acid, phenyl-; Benzenacetic acid; Benzeneacetic acid; Benzylcarboxylic acid; Benzylformic acid; Kyselina fenyloctova; Kyselina fenyloctova [Czech]; PHENYL ACETIC ACID; PHENYL-ACETIC ACID; PHENYLACETIC ACID; Phenylacetic acid (natural); Phenylethanoic acid; Phenyllacetic acid; alpha-Toluic acid; omega-Phenylacetic acid; phenylacetate

Indication

Disease Entry	ICD 11	Status	REF
Hepatic encephalopathy	DB99.5	Approved	[1]
Ornithine transcarbamylase deficiency	5C50.AY	Approved	[2]

• Cross-matching ID:
  PubChem CID: 999
  ChEBI ID: ChEBI:30745
  CAS Number: CAS 103-82-2
  TTD Drug ID: DMQ95GE
  VARIDT Drug ID: DR00333

Molecule-Related Drug Atlas

Drug(s) Affected By Serum paraoxonase/arylesterase 2 (PON2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[6]
Selenium	DM25CGV	N. A.	N. A.	Approved	[7]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[8]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[9]
Atorvastatin	DMF28YC	Acute coronary syndrome	BA41	Approved	[10]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[11]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[12]
Rosiglitazone	DMILWZR	Chronic kidney disease	GB61	Approved	[13]
Cupric Sulfate	DMP0NFQ	Fungal infection	1F29-1F2F	Approved	[14]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]

Drug(s) Affected By Serum paraoxonase/lactonase 3 (PON3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[16]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[17]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[9]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[11]
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[18]
Menadione	DMSJDTY	Vitamin K deficiency	5B59	Approved	[19]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Spironolactone	DM2AQ5N	Chronic heart failure	BD1Z	Approved	[16]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Hypertriglyceridemia	5C80.1	Approved	[16]
RTR-003632	DM45NHF	N. A.	N. A.	Phase 2	[20]

Drug(s) Affected By Serum paraoxonase/arylesterase 1 (PON1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Primidone	DM0WX6I	Epilepsy	8A60-8A68	Approved	[21]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[22]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[23]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[24]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[25]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[26]
Panobinostat	DM58WKG	Chronic graft versus host disease		Approved	[27]
Rifampicin	DM5DSFZ	Non-insulin dependent diabetes	5A11	Approved	[28]
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[29]
Gabapentin	DM6T924	Complex partial seizure	8A68.0	Approved	[21]

Molecular Interaction Atlas of This Drug

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Monocarboxylate transporter 3 (SLC16A8)	DT39AOM	MOT3_HUMAN	Substrate	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Biotransformations	[4]
Serum paraoxonase/arylesterase 2 (PON2)	OT55NCTD	PON2_HUMAN	Biotransformations	[4]
Serum paraoxonase/lactonase 3 (PON3)	OT80W9TA	PON3_HUMAN	Biotransformations	[5]

References

• [1] Exposures of Phenylacetic Acid and Phenylacetylglutamine Across Different Subpopulations and Correlation with Adverse Events. Clin Pharmacokinet. 2021 Dec;60(12):1557-1567.
• [2] Glycerol Phenylbutyrate (Ravicti). Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2017 Apr.
• [3] Immunohistochemical and functional characterization of peptide, organic cation, neutral and basic amino acid, and monocarboxylate drug transporters in human ocular tissues. Drug Metab Dispos. 2013 Feb;41(2):466-74.
• [4] Paraoxonase gene cluster variations associated with coronary heart disease in Chinese Han women. Chin Med J (Engl). 2005 Jul 20;118(14):1167-74.
• [5] Cloning, high level expression of human paraoxonase-3 in Sf9 cells and pharmacological characterization of its product. Biochem Pharmacol. 2005 Oct 1;70(7):1019-25. doi: 10.1016/j.bcp.2005.07.004.
• [6] Paraoxonase enzyme protects retinal pigment epithelium from chlorpyrifos insult. PLoS One. 2014 Jun 30;9(6):e101380. doi: 10.1371/journal.pone.0101380. eCollection 2014.
• [7] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [8] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Decreased macrophage paraoxonase 2 expression in patients with hypercholesterolemia is the result of their increased cellular cholesterol content: effect of atorvastatin therapy. Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):175-80. doi: 10.1161/01.ATV.0000104011.88939.06. Epub 2003 Oct 30.
• [11] 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.
• [12] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [13] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [14] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [15] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [16] Human paraoxonases (PON1, PON2, and PON3) are lactonases with overlapping and distinct substrate specificities. J Lipid Res. 2005 Jun;46(6):1239-47. doi: 10.1194/jlr.M400511-JLR200. Epub 2005 Mar 16.
• [17] Temporal changes in gene expression in the skin of patients treated with isotretinoin provide insight into its mechanism of action. Dermatoendocrinol. 2009 May;1(3):177-87.
• [18] Cannabidiol Displays Proteomic Similarities to Antipsychotics in Cuprizone-Exposed Human Oligodendrocytic Cell Line MO3.13. Front Mol Neurosci. 2021 May 28;14:673144. doi: 10.3389/fnmol.2021.673144. eCollection 2021.
• [19] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [20] Effects of PON polymorphisms and haplotypes on molecular phenotype in Mexican-American mothers and children. Environ Mol Mutagen. 2011 Mar;52(2):105-16. doi: 10.1002/em.20567.
• [21] Antiepileptic drugs: impacts on human serum paraoxonase-1. J Biochem Mol Toxicol. 2017 Jun;31(6).
• [22] Beneficial effect of oleoylated lipids on paraoxonase 1: protection against oxidative inactivation and stabilization. Biochem J. 2003 Oct 15;375(Pt 2):275-85.
• [23] Serum paraoxonase activity before and after treatment of thyrotoxicosis. Clin Endocrinol (Oxf). 2004 Jan;60(1):75-80.
• [24] Effects of some antibiotics on paraoxonase from human serum in vitro and from mouse serum and liver in vivo. Biol Pharm Bull. 2006 Aug;29(8):1559-63.
• [25] Simvastatin modulates expression of the PON1 gene and increases serum paraoxonase: a role for sterol regulatory element-binding protein-2. Arterioscler Thromb Vasc Biol. 2003 Nov 1;23(11):2083-9. doi: 10.1161/01.ATV.0000096207.01487.36. Epub 2003 Sep 18.
• [26] Dietary polyphenols increase paraoxonase 1 gene expression by an aryl hydrocarbon receptor-dependent mechanism. Mol Cell Biol. 2004 Jun;24(12):5209-22.
• [27] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [28] Transcriptional regulation of human paraoxonase 1 by PXR and GR in human hepatoma cells. Toxicol In Vitro. 2015 Dec 25;30(1 Pt B):348-54.
• [29] Induction of paraoxonase 1 and apolipoprotein A-I gene expression by aspirin. J Lipid Res. 2008 Oct;49(10):2142-8.