Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTHCRLEC)

• DOT Name: Prostaglandin G/H synthase 1 (PTGS1)
• Synonyms: EC 1.14.99.1; Cyclooxygenase-1; COX-1; Prostaglandin H2 synthase 1; PGH synthase 1; PGHS-1; PHS 1; Prostaglandin-endoperoxide synthase 1
• Gene Name: PTGS1
• Related Disease: Platelet-type bleeding disorder 12
• UniProt ID: PGH1_HUMAN
• PDB ID: 6Y3C
• EC Number: 1.14.99.1
• Pfam ID: PF03098
• Sequence:
  MSRSLLLWFLLFLLLLPPLPVLLADPGAPTPVNPCCYYPCQHQGICVRFGLDRYQCDCTR
  TGYSGPNCTIPGLWTWLRNSLRPSPSFTHFLLTHGRWFWEFVNATFIREMLMRLVLTVRS
  NLIPSPPTYNSAHDYISWESFSNVSYYTRILPSVPKDCPTPMGTKGKKQLPDAQLLARRF
  LLRRKFIPDPQGTNLMFAFFAQHFTHQFFKTSGKMGPGFTKALGHGVDLGHIYGDNLERQ
  YQLRLFKDGKLKYQVLDGEMYPPSVEEAPVLMHYPRGIPPQSQMAVGQEVFGLLPGLMLY
  ATLWLREHNRVCDLLKAEHPTWGDEQLFQTTRLILIGETIKIVIEEYVQQLSGYFLQLKF
  DPELLFGVQFQYRNRIAMEFNHLYHWHPLMPDSFKVGSQEYSYEQFLFNTSMLVDYGVEA
  LVDAFSRQIAGRIGGGRNMDHHILHVAVDVIRESREMRLQPFNEYRKRFGMKPYTSFQEL
  VGEKEMAAELEELYGDIDALEFYPGLLLEKCHPNSIFGESMIEIGAPFSLKGLLGNPICS
  PEYWKPSTFGGEVGFNIVKTATLKKLVCLNTKTCPYVSFRVPDASQDDGPAVERPSTEL
• Function: Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells (Probable). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products.
• KEGG Pathway:
  Arachidonic acid metabolism (hsa00590)
  Metabolic pathways (hsa01100)
  Platelet activation (hsa04611)
  Serotonergic sy.pse (hsa04726)
  Regulation of lipolysis in adipocytes (hsa04923)
• Reactome Pathway:
  Synthesis of Prostaglandins (PG) and Thromboxanes (TX) (R-HSA-2162123)
  COX reactions (R-HSA-140180)
• BioCyc Pathway: MetaCyc:HS01815-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Platelet-type bleeding disorder 12	DISX055E	Limited	Semidominant	[1]

This DOT Affected the Drug Response of 4 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Aspirin	DM672AH	Approved	Prostaglandin G/H synthase 1 (PTGS1) decreases the response to substance of Aspirin.	[46]
Methamphetamine	DMPM4SK	Approved	Prostaglandin G/H synthase 1 (PTGS1) increases the response to substance of Methamphetamine.	[47]
NAFAZATROM	DM31CV2	Terminated	Prostaglandin G/H synthase 1 (PTGS1) increases the Adverse drug reaction ADR of NAFAZATROM.	[49]
Methylenedioxyamphetamine	DMP204G	Investigative	Prostaglandin G/H synthase 1 (PTGS1) increases the response to substance of Methylenedioxyamphetamine.	[47]

This DOT Affected the Biotransformations of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Dinoprostone	DMTYOPD	Approved	Prostaglandin G/H synthase 1 (PTGS1) increases the chemical synthesis of Dinoprostone.	[48]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE	DMNQL17	Investigative	Prostaglandin G/H synthase 1 (PTGS1) increases the metabolism of 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE.	[50]

63 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[6]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[9]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Prostaglandin G/H synthase 1 (PTGS1).	[13]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[15]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[16]
Isotretinoin	DM4QTBN	Approved	Isotretinoin decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[3]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[17]
Diclofenac	DMPIHLS	Approved	Diclofenac decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[18]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[18]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[19]
Gemcitabine	DMSE3I7	Approved	Gemcitabine decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[20]
Mifepristone	DMGZQEF	Approved	Mifepristone decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[21]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[3]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[18]
Rofecoxib	DM3P5DA	Approved	Rofecoxib decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[4]
Penicillamine	DM40EF6	Approved	Penicillamine increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[22]
Flurbiprofen	DMGN4BY	Approved	Flurbiprofen decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[23]
Naproxen	DMZ5RGV	Approved	Naproxen decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[24]
Etodolac	DM6WJO9	Approved	Etodolac decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[25]
Bupivacaine	DM4PRFC	Approved	Bupivacaine increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[26]
Ketorolac	DMI4EL5	Approved	Ketorolac decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[4]
Flupentixol	DM0DJ9O	Approved	Flupentixol decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[27]
Lornoxicam	DMYZFXN	Approved	Lornoxicam decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[28]
Aminophenazone	DMY2AH1	Phase 4	Aminophenazone decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[18]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[29]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[30]
Epigallocatechin gallate	DMCGWBJ	Phase 3	Epigallocatechin gallate decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[30]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[30]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[30]
CHF-5074	DMTE071	Phase 2	CHF-5074 decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[31]
PMID26394986-Compound-22	DM43Z1G	Patented	PMID26394986-Compound-22 decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[18]
Ferulic Acid	DMJC7NF	Patented	Ferulic Acid decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[30]
Phenacetin	DMRQAM0	Withdrawn from market	Phenacetin decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[18]
Geldanamycin	DMS7TC5	Discontinued in Phase 2	Geldanamycin decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[10]
Celastrol	DMWQIJX	Preclinical	Celastrol increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[33]
Nimesulide	DMR1NMD	Terminated	Nimesulide increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[34]
NS398	DMINUWH	Terminated	NS398 decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[35]
SC-58125	DM874YU	Terminated	SC-58125 decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[25]
Flosulide	DM6OIJ1	Terminated	Flosulide decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[36]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[37]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[38]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[39]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[9]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[40]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[41]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[42]
Arachidonic acid	DMUOQZD	Investigative	Arachidonic acid increases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[43]
all-trans-4-oxo-retinoic acid	DMM2R1N	Investigative	all-trans-4-oxo-retinoic acid decreases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[3]
PAF	DMRZAQW	Investigative	PAF increases the expression of Prostaglandin G/H synthase 1 (PTGS1).	[44]
SC-560	DMT1GJL	Investigative	SC-560 decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[45]
Phenazone	DMCE985	Investigative	Phenazone decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[18]
DFU	DMUM84K	Investigative	DFU decreases the activity of Prostaglandin G/H synthase 1 (PTGS1).	[25]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Prostaglandin G/H synthase 1 (PTGS1).	[32]

References

• [1] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [2] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [3] Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
• [4] Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation. Pain. 2007 Jun;129(3):279-86.
• [5] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [6] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [7] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Quercetin reduces oxidative damage induced by paraquat via modulating expression of antioxidant genes in A549 cells. J Appl Toxicol. 2013 Dec;33(12):1460-7. doi: 10.1002/jat.2812. Epub 2012 Sep 20.
• [10] Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration. Arch Toxicol. 2016 Jan;90(1):159-80.
• [11] Immediate up-regulation of the calcium-binding protein S100P and its involvement in the cytokinin-induced differentiation of human myeloid leukemia cells. Biochim Biophys Acta. 2005 Sep 10;1745(2):156-65.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [14] Progesterone regulation of implantation-related genes: new insights into the role of oestrogen. Cell Mol Life Sci. 2007 Apr;64(7-8):1009-32.
• [15] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [16] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [17] Increased sensitivity for troglitazone-induced cytotoxicity using a human in vitro co-culture model. Toxicol In Vitro. 2009 Oct;23(7):1387-95.
• [18] Cloning, expression, and functional characterization of human cyclooxygenase-1 splicing variants: evidence for intron 1 retention. J Pharmacol Exp Ther. 2005 Dec;315(3):1298-305.
• [19] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [20] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [21] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [22] D-Penicillamine targets metastatic melanoma cells with induction of the unfolded protein response (UPR) and Noxa (PMAIP1)-dependent mitochondrial apoptosis. Apoptosis. 2012 Oct;17(10):1079-94.
• [23] Selective COX-2 inhibitors modulate cellular senescence in human dermal fibroblasts in a catalytic activity-independent manner. Mech Ageing Dev. 2008 Dec;129(12):706-13.
• [24] Pharmacodynamic of cyclooxygenase inhibitors in humans. Prostaglandins Other Lipid Mediat. 2007 Jan;82(1-4):85-94.
• [25] Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. Br J Pharmacol. 1997 May;121(1):105-17.
• [26] The differential effects of bupivacaine and lidocaine on prostaglandin E2 release, cyclooxygenase gene expression and pain in a clinical pain model. Anesth Analg. 2008 Jan;106(1):321-7, table of contents.
• [27] Mitochondrial involvement in schizophrenia and other functional psychoses. Neurochem Res. 1996 Sep;21(9):995-1004.
• [28] 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.
• [29] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [30] Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem Biol Interact. 2010 Dec 5;188(3):659-67.
• [31] In vitro and in vivo profiling of CHF5022 and CHF5074 Two beta-amyloid1-42 lowering agents. Pharmacol Res. 2007 Apr;55(4):318-28.
• [32] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [33] The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells. J Biol Chem. 2015 Jan 16;290(3):1623-38.
• [34] Nimesulide and indomethacin induce apoptosis in head and neck cancer cells. J Oral Pathol Med. 2004 Nov;33(10):607-13.
• [35] Synthetic and naturally occurring COX-2 inhibitors suppress proliferation in a human oesophageal adenocarcinoma cell line (OE33) by inducing apoptosis and cell cycle arrest. Carcinogenesis. 2004 Oct;25(10):1945-52.
• [36] Bisphenol A and bisphenol S induce distinct transcriptional profiles in differentiating human primary preadipocytes. PLoS One. 2016 Sep 29;11(9):e0163318.
• [37] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [38] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [39] mRNA induction and cytokine release of inflammatory mediators during in vitro exposure of human nasal respiratory epithelia to acetaldehyde. Inhal Toxicol. 2006 Dec;18(14):1083-90.
• [40] Imbalance in the antioxidant defence system and pro-genotoxic status induced by high glucose concentrations: In vitro testing in human liver cells. Toxicol In Vitro. 2020 Dec;69:105001. doi: 10.1016/j.tiv.2020.105001. Epub 2020 Sep 15.
• [41] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.
• [42] Cytokine responses of intestinal epithelial-like Caco-2 cells to non-pathogenic and opportunistic pathogenic yeasts in the presence of butyric acid. Biosci Biotechnol Biochem. 2007 Oct;71(10):2428-34.
• [43] Resveratrol inhibits prostaglandin formation in IL-1beta-stimulated SK-N-SH neuronal cells. J Neuroinflammation. 2009 Sep 14;6:26.
• [44] Oxidized phospholipid: POVPC binds to platelet-activating-factor receptor on human macrophagesImplications in atherosclerosis. Atherosclerosis. 2006 Oct;188(2):433-43.
• [45] Gene modulation by Cox-1 and Cox-2 specific inhibitors in human colorectal carcinoma cancer cells. Carcinogenesis. 2004 Mar;25(3):349-57.
• [46] Polymorphisms of COX-1 and GPVI associate with the antiplatelet effect of aspirin in coronary artery disease patients. Thromb Haemost. 2006 Feb;95(2):253-9. doi: 10.1160/TH05-07-0516.
• [47] Human prostaglandin H synthase (hPHS)-1 and hPHS-2 in amphetamine analog bioactivation, DNA oxidation, and cytotoxicity. Toxicol Sci. 2011 Mar;120(1):154-62.
• [48] Kinase-dependent, retinoic acid receptor-independent up-regulation of cyclooxygenase-2 by all-trans retinoic acid in human mesangial cells. Br J Pharmacol. 2006 Sep;149(2):215-25.
• [49] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [50] Carcinogen substrate specificity of human COX-1 and COX-2. Carcinogenesis. 2001 Jan;22(1):5-10. doi: 10.1093/carcin/22.1.5.