50-78-2BSYNRYMUTXBXSQ-UHFFFAOYSA-NBSYNRYMUTXBXSQ-UHFFFAOYSA-N
AspirinAcetylsalicylic acid
Benzoic acid, 2-(acetyloxy)-
2-(ACETYLOXYBENZOIC) ACID
2-(Acetyloxy)benzoic acid
2-Acetoxybenzoic acid
2-Carboxyphenyl acetate
A.S.A. Empirin
Acenterine
Acetard
Aceticyl
Acetilum acidulatum
Acetisal
Acetonyl
Acetophen
Acetosal
Acetosalic acid
Acetosalin
Acetylin
Acetylsal
ACETYLSALICYLSAEURE
Acetyonyl
Acetysal
Acide O-acetylsalicylique
acido O-acetilsalicilico
Acidum acetylsalicylicum
Acimetten
Acylpyrin
Albyl E
Asaflow
Asagran
Asatard
Ascolong
Ascriptin
Aspalon
Aspergum
Aspirdrops
Aspirina 03
Aspirin-Direkt
Aspro Clear
Aspropharm
Asteric
Benaspir
Bialpirina
Bialpirinia
Cardioaspirina
Claradin
Colfarit
Contrheuma Retard
Coricidin
Coricidin D
Dolean pH 8
Dominal
Duramax
Easprin
Ecotrin
Empirin
Endosprin
Endydol
Entericin
Enterophen
Enterosarine
Entrophen
Gelprin
Globentyl
Globoid
Helicon
Idragin
Istopirin
Kapsazal
Magnecyl
Measurin
Medisyl
Melhoral
Micristin
Miniasal
Neuronika
NSC 27223
NSC 406186
Nu-seals
o-(Acetyloxy)benzoic acid
o-Acetoxybenzoic acid
O-acetylsalicylic acid
O-Acetylsalicylsaure
o-Carboxyphenyl acetate
Persistin
Polopiryna
Rheumintabletten
Rhodine
Rhodine 2312
Rhodine NC RP
Salacetin
Salcetogen
Saletin
Salicylic acid acetate
SALICYLIC ACID, ACETYL-
Salospir
Salycylacetylsalicylic acid
Solpyron
Temperal
Triple-sal
Trombyl
Zorprin
DTXSID502010815307-79-6KPHWPUGNDIVLNH-UHFFFAOYSA-MKPHWPUGNDIVLNH-UHFFFAOYSA-M
Diclofenac sodiumBenzeneacetic acid, 2-[(2,6-dichlorophenyl)amino]-, monosodium salt
[2-[(2,6-dichlorophenyl)amino]phenyl]acetate de sodium
[2-[(2,6-diclorofenil)amino]fenil]acetato de sodio
[o-(2,6-Dichloroanilino)phenyl]acetic acid sodium salt
{2-[(2,6-Dichlorophenyl)amino]phenyl}acetate de sodium
2-(2,6-Dichloroanilino)phenylacetic acid sodium salt
2-[(2,6-Dichlorophenyl)amino]benzene acetic acid monosodium salt
Acetic acid, [o-(2,6-dichloroanilino)phenyl]-, monosodium salt
Allvoran
Assaren
Benfofen
Benzeneacetic acid, 2-[(2,6-dichlorophenyl)amino]-, sodium salt (1:1)
Cataflam
Delphimix
Diacron
Dichronic
Diclobene
Diclobenin
Diclodyn
Diclofen SR 100
Diclofenac sodium salt
Diclofenac-Na Emulgel
Diclofenacsodium Emulgel
Diclokalium
Diclophenac sodium
Diclo-Phlogont
Diclo-Puren
Diclord
Diclorep
Dicloreum
Diklovit
Dolobasan
Duravolten
Dyloject
Effekton
Evofenac
Feloran
Fortfen
Hyanalgese D
Inflaban
Kriplex
N-(2,6-Dichlorophenyl)-o-aminophenylacetic acid sodium salt
Natrium-[2-[(2,6-dichlorphenyl)amino]phenyl]acetat
Neriodin
Novapirina
Orthofen
Orthophen
Primofenac
Profenac
Prophenatin
Rhumalgan
sodium [2-[(2,6-dichlorophenyl)amino]phenyl]acetate
Sodium [o-(2,6-dichloroanilino)phenyl]acetate
Sodium 2-(2,6-dichloroanilino)-phenyl-acetate
Sodium diclofenac
Sorelmon
Tsudohmin
Valetan
Voltaren
Voltaren Ophtha
Voltaren Ophtha CD
Voltarol
Voveran
DTXSID303720853-86-1CGIGDMFJXJATDK-UHFFFAOYSA-NCGIGDMFJXJATDK-UHFFFAOYSA-N
Indomethacin1H-Indole-3-acetic acid, 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-
[1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid
1-(4-Chlorobenzoyl)-2-methyl-5-methoxyindole-3-acetic acid
1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid
1-(4-Chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid
1-(p-Chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetic acid
1-(p-Chlorobenzoyl)-2-methyl-5-methoxyindole-3-acetic acid
1-(p-Chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetic acid
1-(p-Chlorobenzoyl)-5-methoxy-2-methylindole-3-acetic acid
Artracin
Artrinovo
Artrivia
Bonidin
Bonidon Gel
Chibro-Amuno
Chrono-Indicid
Chrono-Indocid 75
Confortid
Dolcidium
Dolcidium PL
Dolovin
Durametacin
Elmetacin
Idomethine
Imbrilon
Indacin
Indocid
Indocin
Indocollyre
Indole-3-acetic acid, 1-(p-chlorobenzoyl)-5-methoxy-2-methyl-
Indomecol
Indomed
Indomee
indometacin
indometacina
Indometacine
Indomethacine
Indomethine
Indomod
Indonol
Indo-Phlogont
Indoptic
Indoptol
Indo-Rectolmin
Indorektal
IndoRich
Indo-Tablinen
Indoxen
Inflazon
Infrocin
Innamit
Inteban
Inteban SP
Metacen
Metartril
Methazine
Metindol
Mezolin
Mikametan
Mobilan
N-(p-Chlorobenzoyl)-2-methyl-5-methoxy-3-indolylacetic acid
NSC 77541
Reumacide
Rheumacin LA
Sadoreum
Vital Vitacid
α-[1-(p-Chlorobenzoyl)-2-methyl-5-methoxy-3-indolyl]acetic acid
DTXSID902074022204-53-1CMWTZPSULFXXJA-VIFPVBQESA-NCMWTZPSULFXXJA-VIFPVBQESA-N
Naproxen2-Naphthaleneacetic acid, 6-methoxy-α-methyl-, (αS)-
(+)-(S)-Naproxen
(+)-2-(6-Methoxy-2-naphthyl)propionic acid
(+)-6-Methoxy-α-methyl-2-naphthaleneacetic acid
(+)-Naproxen
(S)-(+)-2-(6-Methoxy-2-naphthyl)propionic acid
(S)-(+)-Naproxen
(S)-(+)-Naproxene
(S)-2-(6-Methoxy-2-naphthyl)propanoic acid
(S)-2-(6-Methoxy-2-naphthyl)propionic acid
(S)-2-(6-Methoxynaphthalen-2-yl)propanoic acid
(S)-2-(6-Methoxynaphthalen-2-yl)propionic acid
(S)-6-Methoxy-α-methyl-2-naphthaleneacetic acid
(S)-Naproxen
(S)-α-Methyl-6-methoxynaphthalene-2-acetic acid
2-Naphthaleneacetic acid, 6-methoxy-α-methyl-, (+)-
2-Naphthaleneacetic acid, 6-methoxy-α-methyl-, (S)-
Apo-Naproxen
Aproxen
d-2-(6-Methoxy-2-naphthyl)propionic acid
Diocodal
d-Naproxen
Dysmenalgit
Equiproxen
Floginax
Laraflex
Naprium
Naprius
Naprosyn
Naprosyne
naproxene
naproxeno
Nycopren
Panoxen
Proxine
Veradol
DTXSID404068615687-27-1HEFNNWSXXWATRW-UHFFFAOYNA-NHEFNNWSXXWATRW-UHFFFAOYSA-N
IbuprofenBenzeneacetic acid, α-methyl-4-(2-methylpropyl)-
(.+-.)-2-(p-Isobutylphenyl)propionic acid
(.+-.)-Ibuprofen
(.+-.)-Ibuprophen
(.+-.)-α-Methyl-4-(2-methylpropyl)benzeneacetic acid
(4-Isobutylphenyl)-α-methylacetic acid
(RS)-Ibuprofen
2-(4-Isobutylphenyl)propanoic acid
2-(4'-Isobutylphenyl)propionic acid
2-(4-Isobutylphenyl)propionic acid
2-(p-Isobutylphenyl)propionic acid
4-Isobutylhydratropic acid
4-Isobutyl-α-methylphenylacetic acid
Actiprofen
Algi-Flanderil
Algiflex
Algofen
Amibufen
Anflagen
Antarene
Antiflam
Apo-Ibuprofen
Apsifen
Artofen
Balkaprofen
Betaprofen
Brufanic
Brufen Retard
Bruflam
Brufort
Buburone
Buluofen
Butacortelone
Butylenin
Codral Period Pain
Combiflam
Dansida
Dentigoa
Dibufen
dl-Ibuprofen
Dolgirid
Dolmaral
Dolocyl
Dolo-Dolgit
Dolofen
Dolofen F
Dolomax
Donjust B
Doretrim
Dorival
Easifon
Epobron
Femadon
Fenspan
Gynofug
Haltran
Hydratropic acid, p-isobutyl-
Ibosure
Ibu-Attritin
Ibuflamar
Ibugesic
Ibuleve
Ibulgan
Ibumetin
Ibupirac
Ibupril
Ibuprocin
Ibuprofene
ibuprofeno
Ibuprohm
Ibu-slow
Ibu-Tab
Inabrin
Iprogel
Lamidon
Librofem
Lidifen
Mensoton
Motrin IB
Mynosedin
Nagifen-D
Napacetin
Nobafon
Nobfelon
Noritis
Novogent
Novoprofen
NSC 256857
Nurofen
Optifen
Opturem
Ostarin
Ostofen
p-(2-Methylpropyl)-α-methylphenylacetic acid
Paduden
Panafen
Pantrop
Paxofen
Pediaprofen
Perofen
PHENYLACETIC ACID, 2-METHYL-4-(2-METHYLPROPYL)-
p-Isobutyl-2-phenylpropionic acid
p-Isobutylhydratropic acid
Proartinal
Proflex
Prontalgin
Quadrax
Ranofen
Recidol
Relcofen
Roidenin
Seclodin
Suspren
Syntofene
Tabalon
Tabalon 400
Tatanal
Trendar
Unipron
Uprofen
α-(4-Isobutylphenyl)propionic acid
α-Methyl-4-(2-methylpropyl)benzeneacetic acid
DTXSID5020732155569-91-8Emamectin benzoate4''-Epimethylamino-4''-deoxyavermectin B1a and B1b benzoates
Avermectin B1, 4''-deoxy-4''-(methylamino)-, (4''R)-, benzoate (1:1)
DTXSID0034566100-00-5CZGCEKJOLUNIFY-UHFFFAOYSA-NCZGCEKJOLUNIFY-UHFFFAOYSA-N
1-Chloro-4-nitrobenzeneBenzene, 1-chloro-4-nitro-
p-Chloronitrobenzene
4-Chloronitrobenzene
1-Chlor-4-nitrobenzol
1-cloro-4-nitrobenceno
1-Nitro-4-chlorobenzene
4-Chloro-1-nitrobenzene
4-Nitro-1-chlorobenzene
4-Nitrochlorobenzene
4-Nitrophenyl chloride
NSC 9792
P-CHLORNITROBENZOL
p-Nitrochlorobenzene
p-Nitrophenyl chloride
DTXSID5020281169590-42-5RZEKVGVHFLEQIL-UHFFFAOYSA-NRZEKVGVHFLEQIL-UHFFFAOYSA-N
CelecoxibBenzenesulfonamide, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]-
4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide
Celebra
Celebrex
Celecox
Celocoxib
DTXSID0022777112281-77-3LQDARGUHUSPFNL-UHFFFAOYNA-NLQDARGUHUSPFNL-UHFFFAOYSA-N
Tetraconazole1H-1,2,4-Triazole, 1-{2-(2,4-dichlorophenyl)-3-(1,1,2,2-tetrafluoroethoxy)propyl}-, (.+-.)-
DTXSID80349562058-46-0UBDNTYUBJLXUNN-IFLJXUKPSA-NUBDNTYUBJLXUNN-IFLJXUKPSA-N
Oxytetracycline hydrochloride2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,5,6,10,12,12a-hexahydroxy-6-methyl-1,11-dioxo-, (4S-(4.alpha.,4a.alpha.,5.alpha.,5a.alpha.,6.beta.,12a.alpha.))-
DTXSID5021097PR:000013427prostaglandin G/H synthase 1PR:000013428prostaglandin G/H synthase 2CHEBI:15551prostaglandin E2CHEBI:39124calcium ionCHEBI:17544hydrogencarbonateUBERON:0005079eggshellGO:0004666prostaglandin-endoperoxide synthase activityGO:0006816calcium ion transportGO:0015701bicarbonate transportGO:0044703multi-organism reproductive process2decreased7functional change4abnormalAceytlsalicylic acid2016-11-29T18:42:082016-11-29T18:42:08Diclofenac sodium2016-11-29T18:42:092016-11-29T18:42:09Indomethacin2016-11-29T18:42:172016-11-29T18:42:17Naproxen2016-11-29T18:42:202016-11-29T18:42:20Ibuprofen2016-11-29T18:42:262016-11-29T18:42:26Emamectin benzoate2016-11-29T18:42:262016-11-29T18:42:261-Chloro-4-nitrobenzene2016-11-29T18:42:262016-11-29T18:42:26169590-42-52016-11-29T18:42:262016-11-29T18:42:26Celecoxib2016-11-29T18:42:262016-11-29T18:42:263-(Difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]-1H-pyrazole2016-11-29T18:42:262016-11-29T18:42:26Tetraconazole2016-11-29T18:42:262016-11-29T18:42:262058-46-02016-11-29T18:42:272016-11-29T18:42:27Oxytetracycline hydrochloride2016-11-29T18:42:272016-11-29T18:42:27Sodium (4-fluoro-2-{[(1S)-1-phenylpropyl]carbamoyl}phenyl)(quinolin-8-ylsulfonyl)azanide2016-11-29T18:42:272016-11-29T18:42:27Inhibition, Cyclooxygenase activityInhibition, Cyclooxygenase activityMolecular<p>Prostaglandin-endoperoxide synthase (PTGS; KEGG ID E.C. 1.14.99.1; <a rel="nofollow" target="_blank" class="external autonumber" href="http://www.genome.jp/dbget-bin/www_bget?ec:1.14.99.1">[1]</a>) is an enzyme that has two catalytic sites. Cyclooxygenase site (COX) catalyzes conversion of arachidonic acid into endoperoxide prostaglandin G2 (<a href="/wiki/index.php?title=Simmons_et_al.,_2004&action=edit&redlink=1" class="new" title="Simmons et al., 2004 (page does not exist)">Simmons et al., 2004</a>). Peroxidase active site converts PGG2 to PGH2 (KEGG reactions 1599, 1590, <a rel="nofollow" target="_blank" class="external autonumber" href="http://www.genome.jp/dbget-bin/www_bget?rn:R01599+R01590+R00073">[2]</a>). PGH2 is a precursor for synthesis of other prostaglandins (e.g., PGEs, PGFs; <a rel="nofollow" target="_blank" class="external autonumber" href="http://www.genome.jp/kegg-bin/show_pathway?scale=1.0&query=prostaglandin&map=map00590&scale=&auto_image=&show_description=hide&multi_query">[3]</a>), prostacyclin and thromboxanes (Simmons et al., 2004; Botting and Botting 2011). Two of the COX isoforms (COX-1 and COX-2) encoded by two different genes (ptgs1 and ptgs2) are well characterized. Ptgs1 is typically expressed constitutively and is involved in maintenance of homeostatic functions. Ptgs2 is largely inducible (e.g., by inflammation, during discrete stages of gamete maturation etc.), but can also be constitutively expressed (e.g., kidney; Green et al, 2012). In mammals, COX-3 (a splice of COX-1) has also been identified (Chandrasekharan et al., 2002), but its function is not well characterized and it is not likely to have prostaglandin producing capacity (Bacchi et al., 2012).
</p><p>Most COX inhibitors interfere with COX site via competitive inhibition (compete for active site with arachidonic acid), but some are capable of covalent modification of COX (Simmons et al., 2004; Willoughby et al., 2011). The inhibition of COX can lead to reduced efficiency of converting arachidonic acid to PGG2. Therefore inhibition of COX can decrease the rate of prostaglandin production (reviewed Simmons et al, 2004; Bacchi et al., 2012).
</p><p>Multiple methods have been developed to investigate inhibition of COX activity - the cyclooxygenase (COX) reaction can be monitored by measurement of oxygen consumption, peroxidase co-substrate oxidation or prostaglandin (PG) detection (e.g., Jang and Pezzuto, 1997; Cuendet et al., 2006). Commercial kits from many suppliers deploying a variety of methods are available for purchase (e.g., Cayman Chemicals, Ann Arbor, MI). Repeatability and reproducibility of these commercial assays is well documented – the data generated by assays is reproducible and interassay variation is typically below 5%. The preparation of fish ovarian tissue for COX activity assay is described by Lister and Van der Kraak (2008).
</p>
<ul>
<li>COX1 activity - US EPA ToxCast assay id: NVS_ENZ_oCOX1
</li>
<li>COX2 activity - US EPA ToxCast assay id: NVS_ENZ_oCOX2
</li>
</ul><p>There is a high level of conservation of this molecular target (i.e., COX), as well as its function, especially across vertebrates (Havird et al., 2008, 2015), indicating that many vertebrate taxa may be susceptible to COX inhibition. Typically, teleost fish genomes contain more than one COX-1 and/or COX -2 gene, likely a result of genome duplication after divergence of teleosts from tetrapods (e.g., Ishikawa et al., 2007; Havird et al., 2015). In invertebrates, COX is found in most crustaceans, the majority of molluscs, but only in specific taxa/lineages within Cnidaria and Annelida. COX genes are not found in Hemichordata, Echinodermata, or Platyhelminthes. Insecta COX genes lack in homology, but may function as COX enzymes based on structural analyses (Havird et al., 2015).
</p>CL:0000255eukaryotic cell<p>Bacchi, S., Palumbo, P., Sponta, A., & Coppolino, M. F. (2012). Clinical pharmacology of non-steroidal anti-inflammatory drugs: a review. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Inflammatory and Anti-Allergy Agents), 11(1), 52-64.
</p><p>Botting, R. M., & Botting, J. H. (2011). C14 Non-steroidal anti-inflammatory drugs. In Principles of Immunopharmacology (pp. 573-584). Birkhäuser Basel.
</p><p>Cao, H., Yu, R., Tao, Y., Nikolic, D., & van Breemen, R. B. (2011). Measurement of cyclooxygenase inhibition using liquid chromatography–tandem mass spectrometry. Journal of pharmaceutical and biomedical analysis, 54(1), 230-235.
</p><p>Chandrasekharan, N. V., Dai, H., Roos, K. L. T., Evanson, N. K., Tomsik, J., Elton, T. S., & Simmons, D. L. (2002). COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proceedings of the National Academy of Sciences,99(21), 13926-13931.
</p><p>Cuendet, M., Mesecar, A. D., DeWitt, D. L., & Pezzuto, J. M. (2006). An ELISA method to measure inhibition of the COX enzymes. Nature protocols,1(4), 1915-1921.
Green, T., Gonzalez, A. A., Mitchell, K. D., & Navar, L. G. (2012). The Complex Interplay between COX-2 and Angiotensin II in Regulating Kidney Function. Current opinion in nephrology and hypertension, 21(1), 7.
</p><p>Havird, J. C., Kocot, K. M., Brannock, P. M., Cannon, J. T., Waits, D. S., Weese, D. A., ... & Halanych, K. M. (2015). Reconstruction of Cyclooxygenase Evolution in Animals Suggests Variable, Lineage-Specific Duplications, and Homologs with Low Sequence Identity. Journal of molecular evolution, 1-16.
</p><p>Havird, J. C., Miyamoto, M. M., Choe, K. P., & Evans, D. H. (2008). Gene duplications and losses within the cyclooxygenase family of teleosts and other chordates. Molecular biology and evolution, 25(11), 2349-2359.
</p><p>Ishikawa, T. O., Griffin, K. J., Banerjee, U., & Herschman, H. R. (2007). The zebrafish genome contains two inducible, functional cyclooxygenase-2 genes.Biochemical and biophysical research communications, 352(1), 181-187.
</p><p>Jang, M. S., & Pezzuto, J. M. (1997). Assessment of cyclooxygenase inhibitors using in vitro assay systems. Methods in cell science, 19(1), 25-31.
</p><p>Kristensen, D. M., Skalkam, M. L., Audouze, K., Lesné, L., Desdoits-Lethimonier, C., Frederiksen, H., ... & Leffers, H. (2011). Many putative endocrine disruptors inhibit prostaglandin synthesis. Environmental health perspectives, 119(4), 534-41.
</p><p>Liedtke, A. J., Crews, B. C., Daniel, C. M., Blobaum, A. L., Kingsley, P. J., Ghebreselasie, K., & Marnett, L. J. (2012). Cyclooxygenase-1-selective inhibitors based on the (E)-2′-des-methyl-sulindac sulfide scaffold. Journal of medicinal chemistry, 55(5), 2287-2300.
</p><p>Lister, A. L., & Van Der Kraak, G. (2008). An investigation into the role of prostaglandins in zebrafish oocyte maturation and ovulation. General and comparative endocrinology, 159(1), 46-57.
</p><p>Simmons, D. L., Botting, R. M., & Hla, T. (2004). Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacological reviews,56(3), 387-437.
</p><p>Willoughby, D. A., Moore, A. R., & Colville-Nash, P. R. (2000). COX-1, COX-2, and COX-3 and the future treatment of chronic inflammatory disease. The Lancet, 355(9204), 646-648.
</p>2016-11-29T18:41:222017-09-16T10:14:42Reduction, Prostaglandin E2 concentrationReduction, Prostaglandin E2 concentrationTissueUBERON:0000178blood2016-11-29T18:41:232017-09-16T10:14:43Reduction, Ca and HCO3 transport to shell glandReduction, Ca and HCO3 transport to shell glandTissueUBERON:0008975oviduct shell gland2016-11-29T18:41:222017-09-16T10:14:43Reduction, Eggshell thicknessReduction, Eggshell thicknessTissueUBERON:0005079eggshell2016-11-29T18:41:222017-09-16T10:14:43N/A, GapN/A, GapTissue<p><span style="color:#FF0000"><b>Do NOT enter any biological descriptions for this key event!</b></span>
This key event is intended as a placeholder for cases where there is a known gap of knowledge that should be noted in an AOP. If you would like to include information specific to your AOP when using this key event, you can include that information on the key event relationship pages that connect this key event to the key events in your AOP.
</p><p><span style="color:#FF0000"><b>Do NOT enter any biological descriptions for this key event!</b></span>
This key event is intended as a placeholder for cases where there is a known gap of knowledge that should be noted in an AOP. If you would like to include information specific to your AOP when using this key event, you can include that information on the key event relationship pages that connect this key event to the key events in your AOP.
</p><p><span style="color:#FF0000"><b>Do NOT enter any biological descriptions for this key event!</b></span>
This key event is intended as a placeholder for cases where there is a known gap of knowledge that should be noted in an AOP. If you would like to include information specific to your AOP when using this key event, you can include that information on the key event relationship pages that connect this key event to the key events in your AOP.
</p>UBERON:0005079eggshell2016-11-29T18:41:222017-09-16T10:14:44N/A, Reproductive failureN/A, Reproductive failureIndividual2016-11-29T18:41:232016-12-03T16:37:490d484153-df9c-4a3c-8abf-75addae3d82a80bde359-d806-4d82-b511-85521ad28e822016-11-29T18:41:332016-12-03T16:37:5480bde359-d806-4d82-b511-85521ad28e8213c924ba-bcbc-4626-ab85-78bb256b5a2b2016-11-29T18:41:332016-12-03T16:37:5513c924ba-bcbc-4626-ab85-78bb256b5a2b20359bd5-1c3a-482a-bc06-25197526ed562016-11-29T18:41:332016-12-03T16:37:5520359bd5-1c3a-482a-bc06-25197526ed565c81c00d-11a8-4063-b6a5-6d69462b1fb22016-11-29T18:41:332016-12-03T16:37:545c81c00d-11a8-4063-b6a5-6d69462b1fb24326337a-0ad9-4823-8db4-a7d4b7c9c2212016-11-29T18:41:332016-12-03T16:37:55Cyclooxygenase inhibition leading reproductive failureCyclooxygenase inhibition leading reproductive failure<p>Dan Villeneuve, US EPA Mid-Continent Ecology Division (villeneuve.dan@epa.gov)</p>
Under Development: Contributions and Comments WelcomeUnder Development1.29<p>Non-steroidal anti-inflammatory drugs have been specifically designed to inhibit cyclooxygenase active site of PTGS; these mechanisms of inhibition are well characterized (Simmons et al, 2004). NSAIDs interfere with COX site via multiple mechanisms including competitive inhibition (most NSAIDs compete for active site with arachidonic acid) and covalent modification (irreversible acetylation) of COX (e.g., aspirin) (Simmons et al., 2004; Willoughby et al., 2011). NSAIDs display different levels of selectivity for the COX-1 vs. COX-2 isoforms (Simmons et al., 2004). Majority of NSAIDs inhibit both isoforms (with variable levels of selectivity for COX-1 vs. COX-2), but several have been designed to preferentially inhibit COX-2 (Bacchi et al., 2012). Recently, COX-1 specific inhibitors have been developed and their therapeutic potential is being explored (Liedtke et al., 2012). Most extensive evidence regarding chemical initiation of this event comes from the mammalian literature and relates to NSAIDs.
</p><p>In addition to NSAIDs, common environmental contaminants of diverse chemical structures and uses (e.g., parabens, phthalates, benzophenones) have been postulated to inhibit prostaglandin synthesis via COX inhibition (Kristensen et al., 2011). U.S. EPA’s high throughput screening program (ACToR, epa.gov) indicated COX as a frequent contaminant target - 61% of 143 tested chemicals inhibited COX-1 and 59% of 106 inhibited COX-2 activity. Several chemicals were either similar in potency (e.g., monobutylphthalate) or more potent than NSAIDs (e.g., insecticide emamectin benzoate and industrial intermediary 1-Chloro-4-nitrobenzene were more potent inhibitors of COX2 than NSAID celecoxib, which was specifically designed to inhibit COX-2). Mechanisms of inhibition for these chemicals are not well elucidated.
</p>adjacentNot SpecifiedModerateadjacentNot SpecifiedNot SpecifiedadjacentNot SpecifiedNot SpecifiedadjacentNot SpecifiedModerateadjacentNot SpecifiedHigh<p><em>Consider the following criteria (may include references to KE Relationship pages): 1. concordance of dose-response relationships; 2. temporal concordance among the key events and adverse effect; 3. strength, consistency, and specificity of association of adverse effect and initiating event; 4. biological plausibility, coherence, and consistency of the experimental evidence; 5. alternative mechanisms that logically present themselves and the extent to which they may distract from the postulated AOP. It should be noted that alternative mechanisms of action, if supported, require a separate AOP; 6. uncertainties, inconsistencies and data gaps. </em></p>
2016-11-29T18:41:162023-04-29T13:02:10