AMFENAC

Details

Stereochemistry	ACHIRAL
Molecular Formula	C15H13NO3
Molecular Weight	255.2686
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=C(C=CC=C1CC(O)=O)C(=O)C2=CC=CC=C2

InChI

InChIKey=SOYCMDCMZDHQFP-UHFFFAOYSA-N

InChI=1S/C15H13NO3/c16-14-11(9-13(17)18)7-4-8-12(14)15(19)10-5-2-1-3-6-10/h1-8H,9,16H2,(H,17,18)

HIDE SMILES / InChI

Molecular Formula	C15H13NO3
Molecular Weight	255.2686
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.drugbank.ca/drugs/DB06802https://www.ncbi.nlm.nih.gov/pubmed/871089
Curator's Comment: Description was created based on several sources, including https://link.springer.com/article/10.1007/BF03299088 | http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=35377 | https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000MedR.pdf | https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021862lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/10850857

Amfenac (AHR 5850) is a non-steroidal anti-inflammatory compound possessing antipyretic and analgesic properties. It is an inhibitor of cyclooxygenases. Amfenac sodium has been on the Japanese market since 1986 (as FENAZOX®, Meiji) in an oral dosage form (50 mg, four-times-daily) indicated for the treatment of pain and inflammation associated with rheumatoid and osteoarthritis and low back pain, as well as the treatment of pain and inflammation following surgery, injury or tooth extraction. Amfenac is an active moiety of nepafenac (amfenac amide), the prodrug has very weak cyclooxygenase inhibitory activity whereas amfenac exhibits more potent cyclooxygenase activity. Nepafenac at a concentration of 0.1% (NEVANAC) was approved for marketing in the US in 2005. Nepafenac is also approved for marketing in the European Union(EU) and Japan as well as over 60 other countries for the treatment of postoperative pain and inflammation associated with cataract surgery.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: http://www.genome.jp/dbget-bin/www_bget?dr:D05143	Inhibitor 8297	64.3 µM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: http://www.genome.jp/dbget-bin/www_bget?dr:D05143	Inhibitor 8297	0.15 µM [IC50]
Cyclooxygenase-1 127 Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10850857	Inhibitor 8297	0.25 µM [IC50]
Cyclooxygenase-2 196 Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10850857	Inhibitor 8297	0.15 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cataract 15 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021862s008lbl.pdf	Palliative		Approved 8429	NEVANAC Approved Use NEVANAC ophthalmic suspension is a nonsteroidal, antiinflammatory prodrug indicated for the treatment of pain and inflammation associated with cataract surgery Launch Date 1.12432316E12
Pain 614 Sources: http://www.rad-ar.or.jp/siori/english/kekka.cgi?n=35377	Primary		Approved 8429	FENAZOX Approved Use FENAZOX CAPSULES (Amfenac sodium hydrate) is usually used to relieve inflammation and pain in chronic rheumatoid arthritis, osteoarthritis, low back pain, shoulder periarthritis, cervico-omo-brachial syndrome, temporomandibular joint disease, post-operative state, post-traumatic state or post-odontectomy state. Launch Date 5.04835211E11

C_max

Value	Dose	Co-administered	Analyte	Population
205.3 ng/mL DRUG LABEL https://iovs.arvojournals.org/article.aspx?articleid=2383342	1 drop single, ocular dose: 1 drop route of administration: Ocular experiment type: SINGLE co-administered:		NEPAFENAC aqueous humor	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.847 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf	1 drop 1 times / day steady-state, ocular dose: 1 drop route of administration: Ocular experiment type: STEADY-STATE co-administered:		NEPAFENAC unknown	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
331.1 ng × h/mL DRUG LABEL https://iovs.arvojournals.org/article.aspx?articleid=2383342	1 drop single, ocular dose: 1 drop route of administration: Ocular experiment type: SINGLE co-administered:		NEPAFENAC aqueous humor	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
1 drop 1 times / day multiple, topical Recommended Dose: 1 drop, 1 times / day Route: topical Route: multiple Dose: 1 drop, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24345529 Page: p.209	unhealthy, 68.7+/- 9.08 n = 817 Health Status: unhealthy Condition: Pain and inflammation associated with cataract surgery Age Group: 68.7+/- 9.08 Sex: M+F Population Size: 817 Sources: https://pubmed.ncbi.nlm.nih.gov/24345529 Page: p.209	Disc. AE: Hypersensitivity... AEs leading to discontinuation/dose reduction: Hypersensitivity (0.12%) Sources: https://pubmed.ncbi.nlm.nih.gov/24345529 Page: p.209
1 drop 1 times / day multiple, topical Recommended Dose: 1 drop, 1 times / day Route: topical Route: multiple Dose: 1 drop, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Pain and inflammation associated with cataract surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf Page: p.1	Disc. AE: Bleeding, Healing delayed... AEs leading to discontinuation/dose reduction: Bleeding Healing delayed Corneal disorder (NOS) Keratitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
Hypersensitivity	0.12% Disc. AE	1 drop 1 times / day multiple, topical Recommended Dose: 1 drop, 1 times / day Route: topical Route: multiple Dose: 1 drop, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24345529 Page: p.209	unhealthy, 68.7+/- 9.08 n = 817 Health Status: unhealthy Condition: Pain and inflammation associated with cataract surgery Age Group: 68.7+/- 9.08 Sex: M+F Population Size: 817 Sources: https://pubmed.ncbi.nlm.nih.gov/24345529 Page: p.209
Bleeding	Disc. AE	1 drop 1 times / day multiple, topical Recommended Dose: 1 drop, 1 times / day Route: topical Route: multiple Dose: 1 drop, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Pain and inflammation associated with cataract surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf Page: p.1
Corneal disorder (NOS)	Disc. AE	1 drop 1 times / day multiple, topical Recommended Dose: 1 drop, 1 times / day Route: topical Route: multiple Dose: 1 drop, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Pain and inflammation associated with cataract surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf Page: p.1
Healing delayed	Disc. AE	1 drop 1 times / day multiple, topical Recommended Dose: 1 drop, 1 times / day Route: topical Route: multiple Dose: 1 drop, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Pain and inflammation associated with cataract surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf Page: p.1
Keratitis	Disc. AE	1 drop 1 times / day multiple, topical Recommended Dose: 1 drop, 1 times / day Route: topical Route: multiple Dose: 1 drop, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Pain and inflammation associated with cataract surgery Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203491s001lbl.pdf Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478 CYP2E1 882 P-gp 1461	CYP 270 P-gp 1537 UGT enzymes 27

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	inconclusive
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	inconclusive	amfenac 4
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 8, 14	no	amfenac 4

Drug as victim

Target	Modality	Activity	Metabolite
CYP 270	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	inconclusive	amfenac 4
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	inconclusive
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	inconclusive	amfenac 4
UGT enzymes 27	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	likely
UGT enzymes 27	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203491Orig1s000ClinPharmR.pdf Page: 14.0	likely	amfenac 4

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:75922	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:75922
ChemicalBook	CB01116872	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB01116872
MolPort	MolPort-003-987-236	https://www.molport.com/shop/molecule-link/MolPort-003-987-236
Selleck Chemicals	Nepafenac	http://www.selleckchem.com/products/Nepafenac.html
ZINC	ZINC000005162311	http://zinc15.docking.org/substances/ZINC000005162311
eMolecules	10510502	https://www.emolecules.com/cgi-bin/more?vid=10510502

PubMed

Title	Date	PubMed
Antiinflammatory agents. 1. Synthesis and antiinflammatory activity of 2-amino-3-benzoylphenylacetic acid.	1979 Sep	490552
Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: II. In vitro bioactivation and permeation of external ocular barriers.	2000 Aug	10850858
Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation: I. Assessment of anti-inflammatory efficacy.	2000 Aug	10850857
Topical nepafenac inhibits ocular neovascularization.	2003 Jan	12506103
Pharmacokinetics of topical ocular drug delivery: potential uses for the treatment of diseases of the posterior segment and beyond.	2003 Jun	12769666
Inflammation-mediated retinal edema in the rabbit is inhibited by topical nepafenac.	2003 Oct	14635785
Comparison of the analgesic efficacy and safety of nepafenac ophthalmic suspension compared with diclofenac ophthalmic solution for ocular pain and photophobia after excimer laser surgery: a phase II, randomized, double-masked trial.	2006 Apr	16750464
New drugs 06, part II.	2006 Aug	16888514
Nepafenac: a unique nonsteroidal prodrug.	2006 Fall	17060788
Ocular permeation and inhibition of retinal inflammation: an examination of data and expert opinion on the clinical utility of nepafenac.	2006 Feb	16466612
New drugs: ramelteon, tipranavir, nepafenac, and deferasirox.	2006 Jan-Feb	16529348
The effect of a selective cyclooxygenase-2 (COX-2) inhibitor on the proliferation rate of retinoblastoma cell lines.	2006 May	16123787
Analgesic and anti-inflammatory effectiveness of nepafenac 0.1% for cataract surgery.	2007 Dec	19668532
Re: Prostaglandin E(2) inhibition and aqueous concentration of ketorolac 0.4% and nepafenac 0.1% in patients undergoing phacoemulsification.	2007 Dec	18036883
Cystoid and diabetic macular edema treated with nepafenac 0.1%.	2007 Dec	18001248
Effects of topical anti-inflammatory agents in a botulinum toxin B-induced mouse model of keratoconjunctivitis sicca.	2007 Feb	17341147
Topical administration of nepafenac inhibits diabetes-induced retinal microvascular disease and underlying abnormalities of retinal metabolism and physiology.	2007 Feb	17259381
Comparative effects of the nonsteroidal anti-inflammatory drug nepafenac on corneal sensory nerve fibers responding to chemical irritation.	2007 Jan	17197531
Nepafenac ophthalmic suspension 0.1% for the prevention and treatment of ocular inflammation associated with cataract surgery.	2007 Jan	17189793
Prostaglandin E2 inhibition and aqueous concentration of ketorolac 0.4% (acular LS) and nepafenac 0.1% (nevanac) in patients undergoing phacoemulsification.	2007 Jul	17601444
Double-masked comparison of ketorolac tromethamine 0.4% versus nepafenac sodium 0.1% for postoperative healing rates and pain control in eyes undergoing surface ablation.	2007 Jul	17592313
Double-masked study of the effects of nepafenac 0.1% and ketorolac 0.4% on corneal epithelial wound healing and pain after photorefractive keratectomy.	2007 Jul-Aug	17901034
Nepafenac-associated corneal melt.	2007 Nov	17964407
Ketorolac tromethamine LS 0.4% versus nepafenac 0.1% in patients having cataract surgery. Prospective randomized double-masked clinical trial.	2007 Nov	17964399
The effects of a cyclooxygenase-2 (COX-2) expression and inhibition on human uveal melanoma cell proliferation and macrophage nitric oxide production.	2007 Nov 27	18042295
Effects of nonsteroidal ophthalmic drops on epithelial healing and pain in patients undergoing bilateral photorefractive keratectomy (PRK).	2007 Nov-Dec	18165210
Case of corneal melting associated with the use of topical nepafenac.	2007 Sep	17721306
Incidence of visually significant pseudophakic macular edema after uneventful phacoemulsification in patients treated with nepafenac.	2007 Sep	17720068
In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac.	2007 Sep	17720067
The use of a cyclooxygenase-2 inhibitor (Nepafenac) in an ocular and metastatic animal model of uveal melanoma.	2007 Sep	17434930
Topical nepafenac in the treatment of diabetic macular edema.	2008 Dec	19668417
Nepafenac dosing frequency for ocular pain and inflammation associated with cataract surgery.	2008 Dec	19040348
Topical ophthalmic NSAIDs: a discussion with focus on nepafenac ophthalmic suspension.	2008 Jun	19668727
Topical ocular delivery of NSAIDs.	2008 Jun	18437583
Amfenac increases the radiosensitivity of uveal melanoma cell lines.	2008 May	18049486
Inhibition of surgically induced miosis and prevention of postoperative macular edema with nepafenac.	2009	19668569
Nepafenac: new drug. After cataract surgery: just another NSAID eye drop. No better than other NSAID eye drops, and less convenient to use.	2009 Aug	19743570
Nepafenac dosing frequency for ocular pain and inflammation associated with cataract surgery.	2009 Aug	19552601
Inflammatory mediators and angiogenic factors in choroidal neovascularization: pathogenetic interactions and therapeutic implications.	2010	20871825
The effects of nepafenac and amfenac on retinal angiogenesis.	2010 Feb 15	19897019
Impact of nepafenac 0.1% on macular thickness and postoperative visual acuity after cataract surgery in patients at low risk for cystoid macular oedema.	2010 Jan	19229275
Randomized clinical trial of treatment for TMJ disc displacement.	2010 Nov	20739691
Nepafenac-assisted mydriasis in a rabbit model.	2010 Oct	20674259

Patents

Sample Use Guides

In Vivo Use Guide

One drop of Nepafenac ophthalmic suspension, 0.3% should be applied to the affected eye one-time-daily beginning 1 day prior to cataract surgery, continued on the day of surgery and through the first 2 weeks of the postoperative period. An additional drop should be administered 30 to 120 minutes prior to surgery.

Route of Administration: Topical

In Vitro Use Guide

Nepafenac exhibited only weak COX-1 inhibitory activity (IC50 = 64.3 uM). However, amfenac, an active metabolite of nepafenac, was a potent inhibitor of COX-1 (IC50 = 0.25 uM) and COX-2 activity (IC50 = 0.15 uM).

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:02:24 UTC 2023` Edited by `admin` on `Fri Dec 15 16:02:24 UTC 2023`
Record UNII	28O5C1J38A
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

AMFENAC

Official Name

English

Amfenac [WHO-DD]

Common Name

English

NSC-309467

Code

English

amfenac [INN]

Common Name

English

AMFENAC [MI]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C257