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

General Information of Drug (ID: DM7EN8I)

Drug Name
Diflunisal Drug Info
Synonyms
Adomal; Algobid; Citidol; Difludol; Diflunisalum; Dolisal; Dolobid; Dolobil; Dolobis; Dolocid; Flovacil; Fluniget; Fluodonil; Flustar; Noaldol; Reuflos; Unisal; Apotex Brand of Diflunisal; Cahill May Roberts Brand of Diflunisal; Diflunisal Novopharm Brand; Frosst SA Brand of Diflunisal; Merck Brand of Diflunisal; Novopharm Brand of Diflunisal; Nu Pharm Brand of Diflunisal; MK 647; MK647; Apo-Diflunisal; Diflunisalum [INN-Latin]; Dolobid (TN); MK-647; Merck Sharp & Dohme Brand of Diflunisal; Novo-Diflunisal; Nu-Diflunisal; Nu-Pharm Brand of Diflunisal; Diflunisal (JAN/USP/INN); Diflunisal [USAN:INN:BAN:JAN]; 2',4'-Difluoro-4-hydroxy-(1,1'-biphenyl)-3-carboxylic acid; 2',4'-Difluoro-4-hydroxy-3-biphenylcarboxylic acid; 2',4'-difluoro-4-hydroxybiphenyl-3-carboxylic acid; 2-(Hydroxy)-5-(2,4-difluorophenyl)benzoic acid; 5-(2,4-DIFLUOROPHENYL)-2-HYDROXY-BENZOIC ACID; 5-(2,4-Difluorophenyl)salicylic acid; 5-(2,4-difluorophenyl)-2-hydroxybenzoic acid; 5-[2,4-Difluorophenyl]salicylic acid
Indication
Disease Entry ICD 11 Status REF
Osteoarthritis FA00-FA05 Approved [1]
Pain MG30-MG3Z Approved [2]
Chronic pain MG30 Investigative [1]
Therapeutic Class
Analgesics
Cross-matching ID
PubChem CID
3059
ChEBI ID
CHEBI:39669
CAS Number
CAS 22494-42-4
TTD Drug ID
DM7EN8I
VARIDT Drug ID
DR00567
INTEDE Drug ID
DR0494
ACDINA Drug ID
D00197

Molecule-Related Drug Atlas

Molecule-Related Drug Atlas
Molecule Type:
DTT
DME
DOT
Drug Status:
Approved Drug(s)
Download the Complete Related Drug List
Drug(s) Targeting Prostaglandin G/H synthase 2 (COX-2)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Ibuprofen DM8VCBE Dysmenorrhea GA34.3 Approved [11]
Naproxen DMZ5RGV Bursitis Approved [12]
Etodolac DM6WJO9 Osteoarthritis FA00-FA05 Approved [13]
Indomethacin DMSC4A7 Bursitis Approved [14]
Celecoxib DM6LOQU Dysmenorrhea GA34.3 Approved [15]
Nabumetone DMAT2XH Osteoarthritis FA00-FA05 Approved [16]
Rofecoxib DM3P5DA Osteoarthritis FA00-FA05 Approved [17]
Flurbiprofen DMGN4BY Osteoarthritis FA00-FA05 Approved [18]
Eicosapentaenoic acid/docosa-hexaenoic acid DMMUCG4 Hypertriglyceridemia 5C80.1 Approved [19]
Aminosalicylic Acid DMENSL5 Crohn disease DD70 Approved [14]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Metabolized By UDP-glucuronosyltransferase 1A1 (UGT1A1)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Tamoxifen DMLB0EZ Breast cancer 2C60-2C65 Approved [20]
Estradiol DMUNTE3 Acne vulgaris ED80 Approved [21]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [22]
Etoposide DMNH3PG Acute myelogenous leukaemia 2A41 Approved [23]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [24]
Valproate DMCFE9I Epilepsy 8A60-8A68 Approved [25]
Mycophenolate mofetil DMPQAGE Hepatosplenic T-cell lymphoma Approved [26]
Metronidazole DMTIVEN Abscess Approved [27]
Propofol DMB4OLE Anaesthesia 9A78.6 Approved [28]
Ethanol DMDRQZU Chronic pain MG30 Approved [29]
⏷ Show the Full List of 10 Drug(s)
Drug(s) Affected By Protein c-Fos (FOS)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Arsenic trioxide DM61TA4 Acute lymphoblastic leukaemia 2A85 Approved [30]
Cannabidiol DM0659E Dravet syndrome 8A61.11 Approved [31]
Verapamil DMA7PEW Angina pectoris BA40 Approved [6]
Sertraline DM0FB1J Coronary heart disease BA80.Z Approved [32]
Acebutolol DM0TI4U Hypertension BA00-BA04 Approved [6]
Fulvestrant DM0YZC6 Breast cancer 2C60-2C65 Approved [33]
Hydrogen peroxide DM1NG5W Infectious disease 1A00-CA43.1 Approved [34]
Methotrexate DM2TEOL Anterior urethra cancer Approved [35]
Simvastatin DM30SGU Arteriosclerosis BD40 Approved [36]
Quercetin DM3NC4M Obesity 5B81 Approved [37]
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Drug(s) Affected By HLA class I histocompatibility antigen, A alpha chain (HLA-A)
Drug Name Drug ID Indication ICD 11 Highest Status REF
Carbamazepine DMZOLBI Epilepsy 8A60-8A68 Approved [38]
Phenytoin DMNOKBV Epilepsy 8A60-8A68 Approved [39]
Allopurinol DMLPAOB Gout FA25 Approved [40]
Acetaminophen DMUIE76 Allergic rhinitis CA08.0 Approved [41]
Clavulanate DM2FGRT Bacteremia 1A73 Approved [42]
Ticlopidine DMO946V Acute coronary syndrome BA41 Approved [43]
Amoxicillin DMUYNEI Acute otitis media AB00 Approved [42]
Tretinoin DM49DUI Acne vulgaris ED80 Approved [44]
Erythromycin DM4K7GQ Acne vulgaris ED80 Approved [5]
Zidovudine DM4KI7O Human immunodeficiency virus infection 1C62 Approved [5]
⏷ Show the Full List of 10 Drug(s)

Molecular Interaction Atlas of This Drug

Molecular Interaction Atlas
Download the Complete Interaction Atlas for Visualization in Cytoscape

Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Prostaglandin G/H synthase 2 (COX-2) TTVKILB PGH2_HUMAN Inhibitor [3]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) Main DME DEYGVN4 UD11_HUMAN Substrate [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
HLA class I histocompatibility antigen, A alpha chain (HLA-A) OTAH14LU HLAA_HUMAN Gene/Protein Processing [5]
Protein c-Fos (FOS) OTJBUVWS FOS_HUMAN Gene/Protein Processing [6]
Transthyretin OTAFXQRA TTHY_HUMAN Protein Interaction/Cellular Processes [7]
UDP-glucuronosyltransferase 1A1 OTH1C8OJ UD11_HUMAN Gene/Protein Processing [8]
UDP-glucuronosyltransferase 1A10 OTOTZVEY UD110_HUMAN Biotransformations [9]
UDP-glucuronosyltransferase 1A3 OTUEOER3 UD13_HUMAN Biotransformations [9]
UDP-glucuronosyltransferase 1A7 OTY4JJ32 UD17_HUMAN Biotransformations [9]
UDP-glucuronosyltransferase 1A8 OTTMABBG UD18_HUMAN Biotransformations [9]
UDP-glucuronosyltransferase 2B7 OT2Q71VQ UD2B7_HUMAN Biotransformations [10]

References

1 Diflunisal FDA Label
2 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: 7162).
3 Celecoxib and rofecoxib. The role of COX-2 inhibitors in dental practice. J Am Dent Assoc. 2001 Apr;132(4):451-6.
4 Differential effects of phenobarbital on ester and ether glucuronidation of diflunisal in rats. J Pharmacol Exp Ther. 1987 Sep;242(3):1013-8.
5 Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
6 Selection of drugs to test the specificity of the Tg.AC assay by screening for induction of the gadd153 promoter in vitro. Toxicol Sci. 2003 Aug;74(2):260-70. doi: 10.1093/toxsci/kfg113. Epub 2003 May 2.
7 In vivo stabilization of mutant human transthyretin in transgenic mice. Amyloid. 2007 Sep;14(3):227-36. doi: 10.1080/13506120701464396.
8 In vitro inhibitory effects of non-steroidal antiinflammatory drugs on UDP-glucuronosyltransferase 1A1-catalysed estradiol 3beta-glucuronidation in human liver microsomes. Biopharm Drug Dispos. 2005 Jan;26(1):35-9.
9 Gastrointestinally distributed UDP-glucuronosyltransferase 1A10, which metabolizes estrogens and nonsteroidal anti-inflammatory drugs, depends upon phosphorylation. J Biol Chem. 2004 Jul 2;279(27):28320-9. doi: 10.1074/jbc.M401396200. Epub 2004 Apr 26.
10 Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther. 1993 Jan;264(1):475-9.
11 Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development. Reprod Toxicol. 2009 Sep;28(2):239-44.
12 Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000 Oct;40(10):1109-20.
13 Membranous nephropathy associated with the relatively selective cyclooxygenase-2 inhibitor, etodolac, in a patient with early rheumatoid arthritis. Intern Med. 2007;46(13):1055-8.
14 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
15 Pfizer. Product Development Pipeline. March 31 2009.
16 Renal effects of nabumetone, a COX-2 antagonist: impairment of function in isolated perfused rat kidneys contrasts with preserved renal function in vivo. Exp Nephrol. 2001;9(6):387-96.
17 Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
18 Flurbiprofen, a cyclooxygenase inhibitor, protects mice from hepatic ischemia/reperfusion injury by inhibiting GSK-3 signaling and mitochondrial permeability transition.Mol Med.2012 Sep 25;18:1128-35.
19 Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod. 2001 Jun;64(6):745-9.
20 Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites. Cancer Res. 2009 Mar 1;69(5):1892-900.
21 Functional characterization of human and cynomolgus monkey UDP-glucuronosyltransferase 1A1 enzymes. Life Sci. 2010 Aug 14;87(7-8):261-8.
22 Effect of UDP-glucuronosyltransferase (UGT) 1A polymorphism (rs8330 and rs10929303) on glucuronidation status of acetaminophen. Dose Response. 2017 Sep 11;15(3):1559325817723731.
23 UDP-glucuronosyltransferase 1A1 is the principal enzyme responsible for etoposide glucuronidation in human liver and intestinal microsomes: structural characterization of phenolic and alcoholic glucuronides of etoposide and estimation of enzyme kinetics. Drug Metab Dispos. 2007 Mar;35(3):371-80.
24 Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected Ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation. J Clin Pharmacol. 2009 Sep;49(9):1079-90.
25 Effect of aging on glucuronidation of valproic acid in human liver microsomes and the role of UDP-glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10. Drug Metab Dispos. 2009 Jan;37(1):229-36.
26 Characterization of rat intestinal microsomal UDP-glucuronosyltransferase activity toward mycophenolic acid. Drug Metab Dispos. 2006 Sep;34(9):1632-9.
27 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
28 Substrate-dependent modulation of UDP-glucuronosyltransferase 1A1 (UGT1A1) by propofol in recombinant human UGT1A1 and human liver microsomes. Basic Clin Pharmacol Toxicol. 2007 Sep;101(3):211-4.
29 Identification and preliminary characterization of UDP-glucuronosyltransferases catalyzing formation of ethyl glucuronide. Anal Bioanal Chem. 2014 Apr;406(9-10):2325-32.
30 Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
31 Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
32 Sertraline induces endoplasmic reticulum stress in hepatic cells. Toxicology. 2014 Aug 1;322:78-88. doi: 10.1016/j.tox.2014.05.007. Epub 2014 May 24.
33 Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004 Apr;32(2):397-414.
34 Microarray analysis of H2O2-, HNE-, or tBH-treated ARPE-19 cells. Free Radic Biol Med. 2002 Nov 15;33(10):1419-32.
35 Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937. Arthritis Res Ther. 2014 Jan 20;16(1):R17. doi: 10.1186/ar4444.
36 Simvastatin inhibits NOR-1 expression induced by hyperlipemia by interfering with CREB activation. Cardiovasc Res. 2005 Aug 1;67(2):333-41. doi: 10.1016/j.cardiores.2005.03.016. Epub 2005 Apr 21.
37 The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells. J Biol Chem. 2004 Jun 25;279(26):27008-16. doi: 10.1074/jbc.M403588200. Epub 2004 Apr 16.
38 HLA-A*3101 and carbamazepine-induced hypersensitivity reactions in Europeans. N Engl J Med. 2011 Mar 24;364(12):1134-43. doi: 10.1056/NEJMoa1013297.
39 Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010 Mar;11(3):349-56. doi: 10.2217/pgs.09.162.
40 Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenet Genomics. 2011 May;21(5):303-7. doi: 10.1097/FPC.0b013e32834282b8.
41 A study of HLA class I and class II 4-digit allele level in Stevens-Johnson syndrome and toxic epidermal necrolysis. Int J Immunogenet. 2011 Aug;38(4):303-9. doi: 10.1111/j.1744-313X.2011.01011.x. Epub 2011 May 4.
42 HLA alleles influence the clinical signature of amoxicillin-clavulanate hepatotoxicity. PLoS One. 2013 Jul 9;8(7):e68111. doi: 10.1371/journal.pone.0068111. Print 2013.
43 Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case-control study. Pharmacogenomics J. 2008 Feb;8(1):29-33. doi: 10.1038/sj.tpj.6500442. Epub 2007 Mar 6.
44 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.