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

General Information of Drug (ID: DMWADLM)

• Drug Name: Diclofenac glucuronide Drug Info
• Synonyms: Diclofenac acyl glucuronide; Diclofenac glucuronide; CHEBI:59609; Diclofenac beta-D-glucosiduronic acid; UNII-C8BEZ13XEN; C8BEZ13XEN; CHEMBL3527338; 64118-81-6; 1-O-({2-[(2,6-dichlorophenyl)amino]phenyl}acetyl)-beta-D-glucopyranuronic acid; Diclofenac acyl-D-glucuronide; Diclofenac O-glucuronide; Epitope ID:131803; Diclofenac-beta-D-glucuronide; SCHEMBL4258872; Diclofenac-acyl-beta-D-glucuronide; BDBM50088512; ZINC35048352; Q27126801; 2-(2,6-Dichloroanilino)phenylacetic acid beta-D-glucopyranuronosyl ester
• Cross-matching ID:
  PubChem CID: 16084218
  ChEBI ID: CHEBI:59609
  CAS Number: CAS 64118-81-6
  TTD Drug ID: DMWADLM
  INTEDE Drug ID: DR2228

Molecule-Related Drug Atlas

Drug(s) Metabolized By Beta-glucuronidase (uidA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PhIP glucuronide	DM7DWZC	N. A.	N. A.	Investigative	[4]

Drug(s) Affected By Interleukin-8 (CXCL8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Hydrocortisone	DMGEMB7	Acne vulgaris	ED80	Approved	[5]
Nicotine	DMWX5CO	Lung cancer	2C25.0	Approved	[6]
Cannabidiol	DM0659E	Dravet syndrome	8A61.11	Approved	[7]
Pantothenic acid	DM091H2	Vitamin deficiency	5B55-5B71	Approved	[8]
Mechlorethamine	DM0CVXA	Chronic myelogenous leukaemia	2A20.0	Approved	[9]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[10]
Fexofenadine	DM17ONX	Allergic rhinitis	CA08.0	Approved	[11]
Hydrogen peroxide	DM1NG5W	Infectious disease	1A00-CA43.1	Approved	[12]
Nitric Oxide	DM1RBYG	Hypertension	BA00-BA04	Approved	[13]
Lumiracoxib	DM1S4AG	Chronic renal failure	GB61.Z	Approved	[11]

Drug(s) Affected By Cytochrome P450 2C8 (CYP2C8)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[14]
Cyclophosphamide	DM4O2Z7	Advanced cancer	2A00-2F9Z	Approved	[15]
Lovastatin	DM9OZWQ	Arteriosclerosis	BD40	Approved	[14]
Ifosfamide	DMCT3I8	Adult central nervous system germ cell tumor		Approved	[15]
Sulfinpyrazone	DMEV954	Gout	FA25	Approved	[16]
Loratadine	DMF3AN7	Allergy	4A80-4A85	Approved	[14]
Zafirlukast	DMHNQOG	Asthma	CA23	Approved	[14]
Ethinyl Estradiol	DMODJ40	Acne vulgaris	ED80	Approved	[14]
Sorafenib	DMS8IFC	Adenocarcinoma	2D40	Approved	[17]
Dabrafenib	DMX6OE3	Melanoma	2C30	Approved	[18]

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Beta-glucuronidase (uidA)	DE7Y39R	A0A2A5L2J1_LACRH	Substrate	[1]
Beta-glucuronidase (uidA)	DE9EXRN	A0A173S5S4_9FIRM	Substrate	[1]
Beta-glucuronidase (uidA)	DECW8T2	A0A076IX12_9BACE	Substrate	[1]
Beta-glucuronidase (uidA)	DEB8PZ0	Q6W7J7_RUMGN	Substrate	[1]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 2C8 (CYP2C8)	OTHCWT42	CP2C8_HUMAN	Biotransformations	[2]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Gene/Protein Processing	[3]
UDP-glucuronosyltransferase 2B7	OT2Q71VQ	UD2B7_HUMAN	Biotransformations	[2]

References

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• [2] Effect of UGT2B7*2 and CYP2C8*4 polymorphisms on diclofenac metabolism. Toxicol Lett. 2018 Mar 1;284:70-78. doi: 10.1016/j.toxlet.2017.11.038. Epub 2017 Dec 2.
• [3] Toxicological evaluation of acyl glucuronides utilizing half-lives, peptide adducts, and immunostimulation assays. Toxicol In Vitro. 2015 Dec 25;30(1 Pt B):241-9.
• [4] Gut microbial beta-glucuronidase and glycerol/diol dehydratase activity contribute to dietary heterocyclic amine biotransformation. BMC Microbiol. 2019 May 16;19(1):99.
• [5] Monomeric and oligomeric flavanols maintain the endogenous glucocorticoid response in human macrophages in pro-oxidant conditions in vitro. Chem Biol Interact. 2018 Aug 1;291:237-244.
• [6] Nicotine up-regulates IL-8 expression in human gingival epithelial cells following stimulation with IL-1 or P. gingivalis lipopolysaccharide via nicotinic acetylcholine receptor signalling. Arch Oral Biol. 2012 May;57(5):483-90. doi: 10.1016/j.archoralbio.2011.10.007. Epub 2011 Nov 25.
• [7] Ca(2+) Signaling and IL-8 Secretion in Human Testicular Peritubular Cells Involve the Cation Channel TRPV2. Int J Mol Sci. 2018 Sep 19;19(9):2829. doi: 10.3390/ijms19092829.
• [8] Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts. Exp Dermatol. 2009 Nov;18(11):969-78. doi: 10.1111/j.1600-0625.2009.00884.x. Epub 2009 Apr 8.
• [9] Nitrogen mustard prevents transport of Fra-1 into the nucleus to promote c-Fos- and FosB-dependent IL-8 induction in injured mouse epidermis. Toxicol Lett. 2020 Feb 1;319:256-263. doi: 10.1016/j.toxlet.2019.10.006. Epub 2019 Oct 19.
• [10] ERE-independent ERalpha target genes differentially expressed in human breast tumors. Mol Cell Endocrinol. 2005 Dec 21;245(1-2):53-9. doi: 10.1016/j.mce.2005.10.003. Epub 2005 Nov 17.
• [11] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [12] Gypenosides protect retinal pigment epithelium cells from oxidative stress. Food Chem Toxicol. 2018 Feb;112:76-85.
• [13] Nitric oxide synthase inhibitors attenuate ozone-induced airway inflammation in guinea pigs. Possible role of interleukin-8. Am J Respir Crit Care Med. 2000 Jan;161(1):249-56. doi: 10.1164/ajrccm.161.1.9804096.
• [14] Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol. 2005 Jan;45(1):68-78.
• [15] Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Pharmacogenetics. 1997 Jun;7(3):211-21.
• [16] Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes. Arch Biochem Biophys. 2003 Jan 1;409(1):32-44.
• [17] Differential inhibition of human CYP2C8 and molecular docking interactions elicited by sorafenib and its major N-oxide metabolite. Chem Biol Interact. 2021 Apr 1;338:109401. doi: 10.1016/j.cbi.2021.109401. Epub 2021 Feb 5.
• [18] Dabrafenib inhibits ABCG2 and cytochrome P450 isoenzymes; potential implications for combination anticancer therapy. Toxicol Appl Pharmacol. 2022 Jan 1;434:115797. doi: 10.1016/j.taap.2021.115797. Epub 2021 Nov 13.