Details of the Drug

General Information of Drug (ID: DMYK490)

• Drug Name: Nepafenac
• Synonyms: Nevanac; AHR-9434; AL-6515

Indication

Disease Entry	ICD 11	Status	REF
Osteoarthritis	FA00-FA05	Approved	[1], [2], [3]

• Drug Type: Small molecular drug
• #Ro5 Violations (Lipinski): 0:
  Molecular Weight (mw); 254.28
  Topological Polar Surface Area (xlogp); 1.9
  Rotatable Bond Count (rotbonds); 4
  Hydrogen Bond Donor Count (hbonddonor); 2
  Hydrogen Bond Acceptor Count (hbondacc); 3
• ADMET Property:
  Metabolism: The drug is metabolized via the intraocular hydrolases [4]
  MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.16854 micromolar/kg/day [5]
• Chemical Identifiers:
  Formula: C15H14N2O2
  IUPAC Name: 2-(2-amino-3-benzoylphenyl)acetamide
  Canonical SMILES: C1=CC=C(C=C1)C(=O)C2=CC=CC(=C2N)CC(=O)N
  InChI: InChI=1S/C15H14N2O2/c16-13(18)9-11-7-4-8-12(14(11)17)15(19)10-5-2-1-3-6-10/h1-8H,9,17H2,(H2,16,18)
  InChIKey: QEFAQIPZVLVERP-UHFFFAOYSA-N
• Cross-matching ID:
  PubChem CID: 151075
  ChEBI ID: CHEBI:75922
  CAS Number: 78281-72-8
  DrugBank ID: DB06802
  TTD ID: D02IHW

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Prostaglandin G/H synthase (COX)	TTK0943	PGH1_HUMAN; PGH2_HUMAN	Inhibitor	[6], [3]

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Nepafenac (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Inotersen	DMJ93CT	Moderate	Increased risk of bleeding by the combination of Nepafenac and Inotersen.	Amyloidosis [5D00]	[17]
Regorafenib	DMHSY1I	Moderate	Increased risk of bleeding by the combination of Nepafenac and Regorafenib.	Colorectal cancer [2B91]	[17]
Ardeparin	DMYRX8B	Moderate	Increased risk of bleeding by the combination of Nepafenac and Ardeparin.	Coronary thrombosis [BA43]	[17]
Tazemetostat	DMWP1BH	Moderate	Increased risk of bleeding by the combination of Nepafenac and Tazemetostat.	Follicular lymphoma [2A80]	[17]
Avapritinib	DMK2GZX	Moderate	Increased risk of bleeding by the combination of Nepafenac and Avapritinib.	Gastrointestinal stromal tumour [2B5B]	[17]
Acalabrutinib	DM7GCVW	Moderate	Increased risk of bleeding by the combination of Nepafenac and Acalabrutinib.	Mature B-cell lymphoma [2A85]	[17]
Ibrutinib	DMHZCPO	Moderate	Increased risk of bleeding by the combination of Nepafenac and Ibrutinib.	Mature B-cell lymphoma [2A85]	[17]
Ponatinib	DMYGJQO	Moderate	Increased risk of bleeding by the combination of Nepafenac and Ponatinib.	Mature B-cell lymphoma [2A85]	[17]
Ruxolitinib	DM7Q98D	Moderate	Increased risk of bleeding by the combination of Nepafenac and Ruxolitinib.	Myeloproliferative neoplasm [2A20]	[17]
Vorapaxar	DMA16BR	Moderate	Increased risk of bleeding by the combination of Nepafenac and Vorapaxar.	Myocardial infarction [BA41-BA43]	[17]
Plicamycin	DM7C8YV	Moderate	Increased risk of bleeding by the combination of Nepafenac and Plicamycin.	Testicular cancer [2C80]	[17]
Brilinta	DMBR01X	Moderate	Increased risk of bleeding by the combination of Nepafenac and Brilinta.	Thrombosis [DB61-GB90]	[17]
Cabozantinib	DMIYDT4	Moderate	Increased risk of bleeding by the combination of Nepafenac and Cabozantinib.	Thyroid cancer [2D10]	[17]
Betrixaban	DM2C4RF	Moderate	Increased risk of bleeding by the combination of Nepafenac and Betrixaban.	Venous thromboembolism [BD72]	[17]

References

• [1] 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: 7564).
• [2] 2005 approvals: Safety first. Nature Reviews Drug Discovery 5, 92-93 (February 2006).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] FDA approval: ado-trastuzumab emtansine for the treatment of patients with HER2-positive metastatic breast cancer. Clin Cancer Res. 2014 Sep 1;20(17):4436-41.
• [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] Topical nepafenac inhibits ocular neovascularization. Invest Ophthalmol Vis Sci. 2003 Jan;44(1):409-15.
• [7] Mechanism of action of paracetamol. Am J Ther. 2005 Jan-Feb;12(1):46-55.
• [8] Diclofenac and NS-398, a selective cyclooxygenase-2 inhibitor, decrease agonist-induced contractions of the pig isolated ureter. Urol Res. 2000 Dec;28(6):376-82.
• [9] Cyclooxygenase inhibitors: instrumental drugs to understand cardiovascular homeostasis and arterial thrombosis. Cardiovasc Hematol Disord Drug Targets. 2008 Dec;8(4):268-77.
• [10] Comparison of the efficacy and tolerability of dexibuprofen and celecoxib in the treatment of osteoarthritis of the hip. Int J Clin Pharmacol Ther. 2003 Apr;41(4):153-64.
• [11] Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H425-32.
• [12] Interactions of PGH synthase isozymes-1 and -2 with NSAIDs. Ann N Y Acad Sci. 1994 Nov 15;744:50-7.
• [13] The aryl propionic acid R-flurbiprofen selectively induces p75NTR-dependent decreased survival of prostate tumor cells. Cancer Res. 2007 Apr 1;67(7):3254-62.
• [14] Aceclofenac spares cyclooxygenase 1 as a result of limited but sustained biotransformation to diclofenac. Clin Pharmacol Ther. 2003 Sep;74(3):222-35.
• [15] The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro. Inflamm Res. 1999 Jul;48(7):369-79.
• [16] Modulation of arachidonic acid metabolism by orally administered morniflumate in man. Agents Actions. 1991 Jul;33(3-4):233-9.
• [17] Product Information. Acular (ketorolac). Allergan Inc, Irvine, CA.