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

General Information of Drug (ID: DM23D7J)

• Drug Name: Tiaprofenic acid Drug Info
• Synonyms: Surgam; Tiaprofensaeure; Acide tiaprofenique; Acido tiaprofenico; Acidum tiaprofenicum; Surgam SR; FC 3001; RU 15060; Acide tiaprofenique [INN-French]; Acido tiaprofenico [INN-Spanish]; Acidum tiaprofenicum [INN-Latin]; Apo-Tiaprofenic Tablets; Dom-tiaprofenic; Surgam (TN); Surgamyl (TN); Tiaprofen (TN); Tiaprofenic acid (JAN/INN); Tiaprofenic-200-Tab; Tiaprofenic-300-Tab; Tiaprofenic acid [INN:BAN:DCF:JAN]; Alpha-methyl-5-benzoyl-2-thienylacetic acid; 2-(5-Benzyl-2-thienyl)propionsaeure; 2-(5-benzoylthiophen-2-yl)propanoic acid; 2-[5-(phenylcarbonyl)-2-thienyl]propanoic acid; 5-Benzoyl-alpha-methyl-2-thiopheneacetic acid; 5-benzoyl-alpha-methylthiophene-2-acetic acid

Indication

Disease Entry	ICD 11	Status	REF
Osteoarthritis	FA00-FA05	Approved	[1]
Pain	MG30-MG3Z	Approved	[2]

• Therapeutic Class: Analgesics
• Cross-matching ID:
  PubChem CID: 5468
  ChEBI ID: CHEBI:32221
  CAS Number: CAS 33005-95-7
  TTD Drug ID: DM23D7J

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	[7]
Naproxen	DMZ5RGV	Bursitis		Approved	[8]
Etodolac	DM6WJO9	Osteoarthritis	FA00-FA05	Approved	[9]
Indomethacin	DMSC4A7	Bursitis		Approved	[10]
Celecoxib	DM6LOQU	Dysmenorrhea	GA34.3	Approved	[11]
Nabumetone	DMAT2XH	Osteoarthritis	FA00-FA05	Approved	[12]
Rofecoxib	DM3P5DA	Osteoarthritis	FA00-FA05	Approved	[13]
Flurbiprofen	DMGN4BY	Osteoarthritis	FA00-FA05	Approved	[14]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Hypertriglyceridemia	5C80.1	Approved	[15]
Aminosalicylic Acid	DMENSL5	Crohn disease	DD70	Approved	[10]

Drug(s) Affected By Nuclear receptor subfamily 1 group I member 2 (NR1I2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[5]
Vidarabine	DM0N85H	Hepatosplenic T-cell lymphoma		Approved	[5]
Beta-carotene	DM0RXBT	Vitamin deficiency	5B55-5B71	Approved	[16]
Fulvestrant	DM0YZC6	Breast cancer	2C60-2C65	Approved	[17]
Secobarbital	DM14RF5	Epilepsy	8A60-8A68	Approved	[18]
Etidronic acid	DM1XHYJ	Bone Paget disease		Approved	[5]
Bromperidol	DM24XYQ	Schizophrenia	6A20	Approved	[5]
Simvastatin	DM30SGU	Arteriosclerosis	BD40	Approved	[19]
Deoxycholic acid	DM3GYAL	Subcutaneous fat disorder	EF02	Approved	[20]
Quercetin	DM3NC4M	Obesity	5B81	Approved	[21]

Drug(s) Affected By Carbonyl reductase 1 (CBR1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arsenic trioxide	DM61TA4	Acute lymphoblastic leukaemia	2A85	Approved	[22]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[23]
Testosterone enanthate	DMB6871	N. A.	N. A.	Approved	[24]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[25]
Ivermectin	DMDBX5F	Intestinal strongyloidiasis due to nematode parasite	1F6B	Approved	[26]
Zoledronate	DMIXC7G	Adenocarcinoma	2D40	Approved	[27]
Diclofenac	DMPIHLS	Chronic renal failure	GB61.Z	Approved	[28]
Acetaminophen	DMUIE76	Allergic rhinitis	CA08.0	Approved	[29]
Phenobarbital	DMXZOCG	Cluster headache	8A81.0	Approved	[30]
Carbamazepine	DMZOLBI	Epilepsy	8A60-8A68	Approved	[28]

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
Carbonyl reductase 1 (CBR1)	OTQ3A541	CBR1_HUMAN	Biotransformations	[4]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Gene/Protein Processing	[5]
UDP-glucuronosyltransferase 2B7	OT2Q71VQ	UD2B7_HUMAN	Biotransformations	[6]

References

• [1] Tiaprofenic acid. A reappraisal of its pharmacological properties and use in the management of rheumatic diseases. Drugs. 1995 Dec;50(6):1050-75.
• [2] Drug information of Tiaprofenic acid, 2008. eduDrugs.
• [3] Effects of tiaprofenic acid on the concentration and metabolism of proteoglycans in normal and degenerating canine articular cartilage. J Clin Pharmacol. 1990 Sep;30(9):808-14.
• [4] Reductive metabolism of tiaprofenic acid by the human liver and recombinant carbonyl reducing enzymes. Chem Biol Interact. 2017 Oct 1;276:121-126. doi: 10.1016/j.cbi.2017.03.006. Epub 2017 Mar 18.
• [5] Screening of a chemical library reveals novel PXR-activating pharmacologic compounds. Toxicol Lett. 2015 Jan 5;232(1):193-202. doi: 10.1016/j.toxlet.2014.10.009. Epub 2014 Oct 16.
• [6] 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.
• [7] Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development. Reprod Toxicol. 2009 Sep;28(2):239-44.
• [8] 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.
• [9] 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.
• [10] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [11] Pfizer. Product Development Pipeline. March 31 2009.
• [12] 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.
• [13] Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
• [14] 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.
• [15] Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod. 2001 Jun;64(6):745-9.
• [16] Induction of PXR-mediated metabolism by beta-carotene. Biochim Biophys Acta. 2005 May 30;1740(2):162-9. doi: 10.1016/j.bbadis.2004.11.013. Epub 2004 Dec 8.
• [17] Lignans, bacteriocides and organochlorine compounds activate the human pregnane X receptor (PXR). Toxicol Appl Pharmacol. 2005 Dec 1;209(2):123-33. doi: 10.1016/j.taap.2005.03.015.
• [18] Identification and validation of novel human pregnane X receptor activators among prescribed drugs via ligand-based virtual screening. Drug Metab Dispos. 2011 Feb;39(2):337-44. doi: 10.1124/dmd.110.035808. Epub 2010 Nov 10.
• [19] Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor. Drug Metab Dispos. 2005 Jul;33(7):924-9.
• [20] Acetylated deoxycholic (DCA) and cholic (CA) acids are potent ligands of pregnane X (PXR) receptor. Toxicol Lett. 2017 Jan 4;265:86-96.
• [21] Stable cellular models of nuclear receptor PXR for high-throughput evaluation of small molecules. Toxicol In Vitro. 2018 Oct;52:222-234.
• [22] Carbonyl reductase 1 offers a novel therapeutic target to enhance leukemia treatment by arsenic trioxide. Cancer Res. 2012 Aug 15;72(16):4214-24.
• [23] 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.
• [24] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [25] 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.
• [26] 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.
• [27] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [28] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [29] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [30] Proteomic analysis of hepatic effects of phenobarbital in mice with humanized liver. Arch Toxicol. 2022 Oct;96(10):2739-2754. doi: 10.1007/s00204-022-03338-7. Epub 2022 Jul 26.