Details of the Drug

General Information of Drug (ID: DM23D7J)

• Drug Name: Tiaprofenic acid
• 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
• Affected Organisms: Humans and other mammals
• ATC Code:
  M01AE11: Tiaprofenic acid
  M01AE: Propionic acid derivatives
  M01A: ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS
  M01: ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
  M: MUSCULO-SKELETAL SYSTEM
  M01AE11: Tiaprofenic acid
  M01AE: Propionic acid derivatives
  M01A: ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS, NON-STEROIDS
  M01: ANTIINFLAMMATORY AND ANTIRHEUMATIC PRODUCTS
  M: MUSCULO-SKELETAL SYSTEM
• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 260.31
  Logarithm of the Partition Coefficient (xlogp); 3.3
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 1
  Hydrogen Bond Acceptor Count (hbondacc); 4
• ADMET Property:
  BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
  Bioavailability: The bioavailability of drug is 90% []
  Clearance: The drug present in the plasma can be removed from the body at the rate of 0.62 mL/min/kg [4]
  Elimination: 2.5% of drug is excreted from urine in the unchanged form [3]
  Half-life: The concentration or amount of drug in body reduced by one-half in 1.5 - 2.5 hours [4]
  Metabolism: The drug is metabolized via the hepatic []
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 38.41515 micromolar/kg/day [5]
  Unbound Fraction: The unbound fraction of drug in plasma is 0.015% [4]
  Vd: Fluid volume that would be required to contain the amount of drug present in the body at the same concentration as in the plasma 0.08 L/kg [4]
• Chemical Identifiers:
  Formula: C14H12O3S
  IUPAC Name: 2-(5-benzoylthiophen-2-yl)propanoic acid
  Canonical SMILES: CC(C1=CC=C(S1)C(=O)C2=CC=CC=C2)C(=O)O
  InChI: InChI=1S/C14H12O3S/c1-9(14(16)17)11-7-8-12(18-11)13(15)10-5-3-2-4-6-10/h2-9H,1H3,(H,16,17)
  InChIKey: GUHPRPJDBZHYCJ-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 5468
  ChEBI ID: CHEBI:32221
  CAS Number: 33005-95-7
  UNII: 1LS1T6R34C
  DrugBank ID: DB01600
  TTD ID: D0S7VO
• Repurposed Drugs (RPD): Click to Jump to the Detailed RPD Information of This Drug

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	[6]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Carbonyl reductase 1 (CBR1)	OTQ3A541	CBR1_HUMAN	Biotransformations	[7]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Gene/Protein Processing	[8]
UDP-glucuronosyltransferase 2B7	OT2Q71VQ	UD2B7_HUMAN	Biotransformations	[9]

Molecular Expression Atlas of This Drug

• The Studied Disease: Osteoarthritis
• ICD Disease Classification: FA00-FA05

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Prostaglandin G/H synthase 2 (COX-2)	DTT	PTGS2	7.93E-04	-0.29	-0.34

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] BDDCS applied to over 900 drugs
• [4] Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
• [5] Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
• [6] 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.
• [7] 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.
• [8] 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.
• [9] 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.