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

General Information of Drug (ID: DMWUIJE)

• Drug Name: Tolmetin Drug Info
• Synonyms: Tolectin; Tolmetina; Tolmetine; Tolmetino; Tolmetinum; Tolmetina [DCIT]; MCN 2559; McN-2559; Tolectin (TN); Tolmetin Sodium, Dihydrate; Tolmetine [INN-French]; Tolmetino [INN-Spanish]; Tolmetinum [INN-Latin]; Tolmetin (USAN/INN); Tolmetin [USAN:BAN:INN]; Acido 1-metil-5-(p-tolnil)-pirrol-2-acetico; Acido 1-metil-5-(p-tolnil)-pirrol-2-acetico [Spanish]; 1-Methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetic acid; 1-Methyl-5-(4-methylbenzoyl)-pyrrole-2-acetic acid; 1-Methyl-5-p-toluoylpyrrole-2-acetic acid; 2-[1-methyl-5-(4-methylbenzoyl)pyrrol-2-yl]acetic acid; 5-(p-Toluoyl)-1-methylpyrrole-2-acetic acid

Indication

Disease Entry	ICD 11	Status	REF
Osteoarthritis	FA00-FA05	Approved	[1]
Rheumatoid arthritis	FA20	Approved	[2]

• Therapeutic Class: Antiinflammatory Agents
• Cross-matching ID:
  PubChem CID: 5509
  ChEBI ID: CHEBI:71941
  CAS Number: CAS 26171-23-3
  TTD Drug ID: DMWUIJE
  ACDINA Drug ID: D00687

Molecule-Related Drug Atlas

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	[3]
Naproxen	DMZ5RGV	Bursitis		Approved	[6]
Etodolac	DM6WJO9	Osteoarthritis	FA00-FA05	Approved	[7]
Indomethacin	DMSC4A7	Bursitis		Approved	[8]
Celecoxib	DM6LOQU	Dysmenorrhea	GA34.3	Approved	[9]
Nabumetone	DMAT2XH	Osteoarthritis	FA00-FA05	Approved	[10]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[11]
Flurbiprofen	DMGN4BY	Osteoarthritis	FA00-FA05	Approved	[12]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Hypertriglyceridemia	5C80.1	Approved	[13]
Aminosalicylic Acid	DMENSL5	Crohn disease	DD70	Approved	[8]

Drug(s) Affected By HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aspirin	DM672AH	Acute coronary syndrome	BA41	Approved	[14]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[5]
Amoxicillin	DMUYNEI	Acute otitis media	AB00	Approved	[5]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[15]
Allopurinol	DMLPAOB	Gout	FA25	Approved	[16]
Ticlopidine	DMO946V	Acute coronary syndrome	BA41	Approved	[17]
Selenium	DM25CGV	N. A.	N. A.	Approved	[18]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[5]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[19]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[20]

Drug(s) Affected By Albumin (ALB)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[21]
Sulfamethoxazole	DMB08GE	Acute otitis media	AB00	Approved	[22]
Tolbutamide	DM02AWV	Advanced cancer	2A00-2F9Z	Approved	[23]
Diazepam	DM08E9O	Alcohol withdrawal		Approved	[24]
Sertraline	DM0FB1J	Coronary heart disease	BA80.Z	Approved	[25]
Methimazole	DM25FL8	Hyperthyroidism	5A02	Approved	[26]
Imipramine	DM2NUH3	Depression	6A70-6A7Z	Approved	[27]
Colchicine	DM2POTE	Acute gout flare	FA25.0	Approved	[28]
Methotrexate	DM2TEOL	Anterior urethra cancer		Approved	[29]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[30]

Drug(s) Affected By HLA class I histocompatibility antigen, alpha chain E (HLA-E)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ofloxacin	DM0VQN3	Acute gonococcal cervicitis		Approved	[5]
Clindamycin	DM15HL8	Acne vulgaris	ED80	Approved	[5]
Selenium	DM25CGV	N. A.	N. A.	Approved	[18]
Ciprofloxacin XR	DM2NLS9	Acute gonococcal cervicitis		Approved	[5]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[5]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[31]
Isotretinoin	DM4QTBN	Acne vulgaris	ED80	Approved	[20]
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[32]
Thalidomide	DM70BU5	Adult T-cell leukemia/lymphoma		Approved	[5]
Testosterone	DM7HUNW	Hot flushes	GA30	Approved	[33]

Molecular Interaction Atlas of This Drug

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 Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[4]
HLA class I histocompatibility antigen, alpha chain E (HLA-E)	OTX1CTFB	HLAE_HUMAN	Gene/Protein Processing	[5]
HLA class II histocompatibility antigen, DQ beta 1 chain (HLA-DQB1)	OTVVI3UI	DQB1_HUMAN	Gene/Protein Processing	[5]

References

• [1] Tolmetin 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: 7311).
• [3] Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development. Reprod Toxicol. 2009 Sep;28(2):239-44.
• [4] Reversible binding of tolmetin, zomepirac, and their glucuronide conjugates to human serum albumin and plasma. J Pharmacokinet Biopharm. 1994 Feb;22(1):19-40. doi: 10.1007/BF02353408.
• [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] 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.
• [7] 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.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Pfizer. Product Development Pipeline. March 31 2009.
• [10] 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.
• [11] Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
• [12] 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.
• [13] Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod. 2001 Jun;64(6):745-9.
• [14] The human leucocyte antigen-DRB1*1302-DQB1*0609-DPB1*0201 haplotype may be a strong genetic marker for aspirin-induced urticaria. Clin Exp Allergy. 2005 Mar;35(3):339-44. doi: 10.1111/j.1365-2222.2004.02197.x.
• [15] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [20] 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.
• [21] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [22] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [23] A protein-coated magnetic beads as a tool for the rapid drug-protein binding study. J Pharm Biomed Anal. 2010 Jul 8;52(3):420-4. doi: 10.1016/j.jpba.2009.06.023. Epub 2009 Jun 18.
• [24] The three recombinant domains of human serum albumin. Structural characterization and ligand binding properties. J Biol Chem. 1999 Oct 8;274(41):29303-10. doi: 10.1074/jbc.274.41.29303.
• [25] Exploring binding properties of sertraline with human serum albumin: Combination of spectroscopic and molecular modeling studies. Chem Biol Interact. 2015 Dec 5;242:235-46. doi: 10.1016/j.cbi.2015.10.006. Epub 2015 Oct 22.
• [26] Low-expressional IGF1 mediated methimazole-induced liver developmental toxicity in fetal mice. Toxicology. 2018 Sep 1;408:70-79. doi: 10.1016/j.tox.2018.07.004. Epub 2018 Jul 7.
• [27] Use of peak decay analysis and affinity microcolumns containing silica monoliths for rapid determination of drug-protein dissociation rates. J Chromatogr A. 2011 Apr 15;1218(15):2072-8. doi: 10.1016/j.chroma.2010.09.070. Epub 2010 Oct 16.
• [28] [Colchicine in chronic liver disease of alcoholic etiology. Double-blind, randomized study of its effects on blood levels of plasma proteins and clinical course in patients]. Rev Assoc Med Bras (1992). 1995 May-Jun;41(3):207-12.
• [29] Editor's Highlight: Modeling Compound-Induced Fibrogenesis In Vitro Using Three-Dimensional Bioprinted Human Liver Tissues. Toxicol Sci. 2016 Dec;154(2):354-367. doi: 10.1093/toxsci/kfw169. Epub 2016 Sep 7.
• [30] Covalent binding of the flavonoid quercetin to human serum albumin. J Agric Food Chem. 2005 May 18;53(10):4194-7. doi: 10.1021/jf050061m.
• [31] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [32] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [33] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.