Details of the Drug

General Information of Drug (ID: DM5ZOX8)

• Drug Name: Benoxaprofen
• Synonyms: Benoxaprofene; Benoxaprofeno; Benoxaprofenum; Coxigon; Inflamid; Opren; Oraflex; Uniprofen; LRCL3794; Lilly 90459; Benoxaprofene [INN-French]; Benoxaprofeno [INN-Spanish]; Benoxaprofenum [INN-Latin]; Dl-Benoxaprofen; Oraflex (TN); Benoxaprofen (USAN/INN); Benoxaprofen [USAN:INN:BAN]; (+-)-2-(p-Chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid; (-)-2-(4-Chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid; (-)-Benoxaprofen; (1)-2-(4-Chlorophenyl)benzoxazole-5-propionic acid; 2-(2-(4-Chlorophenyl)-1,3-benzoxazol-5-yl)propanoic acid; 2-(4-Chlorophenyl)-alpha-methyl-5-benzoxazoleacetic acid; 2-(p-Chlorophenyl)-.alpha.-methyl-5-benzoxazoleacetic acid; 2-[2-(4-Chlorophenyl)-1,3-benzoxazol-5-yl]propanoic acid

Indication

Disease Entry	ICD 11	Status	REF
Inflammation	1A00-CA43.1	Withdrawn from market	[1]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 301.72
  Logarithm of the Partition Coefficient (xlogp); 4.1
  Rotatable Bond Count (rotbonds); 3
  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 [2]
• Chemical Identifiers:
  Formula: C16H12ClNO3
  IUPAC Name: 2-[2-(4-chlorophenyl)-1,3-benzoxazol-5-yl]propanoic acid
  Canonical SMILES: CC(C1=CC2=C(C=C1)OC(=N2)C3=CC=C(C=C3)Cl)C(=O)O
  InChI: InChI=1S/C16H12ClNO3/c1-9(16(19)20)11-4-7-14-13(8-11)18-15(21-14)10-2-5-12(17)6-3-10/h2-9H,1H3,(H,19,20)
  InChIKey: MITFXPHMIHQXPI-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 39941
  ChEBI ID: CHEBI:76114
  CAS Number: 51234-28-7
  DrugBank ID: DB04812
  TTD ID: D00CCI

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Acetoacetyl-CoA thiolase (ACAT1)	TTK3C21	THIL_HUMAN	Inhibitor	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Drug Response	[4]
Beta-glucuronidase (GUSB)	OT9N1DK3	BGLR_HUMAN	Protein Interaction/Cellular Processes	[5]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Gene/Protein Processing	[6]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Gene/Protein Processing	[6]
Polyunsaturated fatty acid 5-lipoxygenase (ALOX5)	OT7FOIK2	LOX5_HUMAN	Gene/Protein Processing	[7]
UDP-glucuronosyltransferase 1A3	OTUEOER3	UD13_HUMAN	Drug Response	[8]
UDP-glucuronosyltransferase 1A9	OTPCHAFX	UD19_HUMAN	Drug Response	[8]
UDP-glucuronosyltransferase 2B7	OT2Q71VQ	UD2B7_HUMAN	Biotransformations	[9]

Molecular Expression Atlas of This Drug

• The Studied Disease: Inflammation
• ICD Disease Classification: 1A00-CA43.1

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Acetoacetyl-CoA thiolase (ACAT1)	DTT	ACAT1	4.99E-05	0.73	1.46

References

• [1] Benoxaprofen: side-effect profile in 300 patients. Br Med J (Clin Res Ed). 1982 May 8;284(6326):1365-8.
• [2] BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
• [3] Inhibition of lyso-PAF: acetyl-CoA acetyltransferase by salicylates and other compounds. Prostaglandins. 1988 Jun;35(6):939-44.
• [4] Benoxaprofen photosensitization of cell membrane disruption. J Invest Dermatol. 1984 Mar;82(3):214-8. doi: 10.1111/1523-1747.ep12260034.
• [5] Effects of benoxaprofen on human neutrophil function. J Rheumatol. 1984 Jun;11(3):265-71.
• [6] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [7] In vitro inhibition of leukotriene B4 formation by exogeneous 5-lipoxygenase inhibitors is associated with enhanced generation of 15-hydroxy-eicosatetraenoic acid (15-HETE) by human neutrophils. Arch Dermatol Res. 1988;280(7):430-6.
• [8] Carboxylic acid drug-induced DNA nicking in HEK293 cells expressing human UDP-glucuronosyltransferases: role of acyl glucuronide metabolites and glycation pathways. Chem Res Toxicol. 2007 Oct;20(10):1520-7. doi: 10.1021/tx700188x. Epub 2007 Sep 20.
• [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.