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Molecule Details

General Information of the Molecule
Name
Prostaglandin G/H synthase 2 (COX-2)
Synonyms
Prostaglandin-endoperoxide synthase 2; Prostaglandin H2 synthase 2; PHS II; PGHS-2; PGH synthase 2; Cyclooxygenase-2; COX2; COX-2
Gene Name
PTGS2
Gene ID
5743
Sequence
MLARALLLCAVLALSHTANPCCSHPCQNRGVCMSVGFDQYKCDCTRTGFYGENCSTPEFL
TRIKLFLKPTPNTVHYILTHFKGFWNVVNNIPFLRNAIMSYVLTSRSHLIDSPPTYNADY
GYKSWEAFSNLSYYTRALPPVPDDCPTPLGVKGKKQLPDSNEIVEKLLLRRKFIPDPQGS
NMMFAFFAQHFTHQFFKTDHKRGPAFTNGLGHGVDLNHIYGETLARQRKLRLFKDGKMKY
QIIDGEMYPPTVKDTQAEMIYPPQVPEHLRFAVGQEVFGLVPGLMMYATIWLREHNRVCD
VLKQEHPEWGDEQLFQTSRLILIGETIKIVIEDYVQHLSGYHFKLKFDPELLFNKQFQYQ
NRIAAEFNTLYHWHPLLPDTFQIHDQKYNYQQFIYNNSILLEHGITQFVESFTRQIAGRV
AGGRNVPPAVQKVSQASIDQSRQMKYQSFNEYRKRFMLKPYESFEELTGEKEMSAELEAL
YGDIDAVELYPALLVEKPRPDAIFGETMVEVGAPFSLKGLMGNVICSPAYWKPSTFGGEV
GFQIINTASIQSLICNNVKGCPFTSFSVPDPELIKTVTINASSSRSGLDDINPTVLLKER
STEL
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Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis. During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, that regulates phagocytic microglia (By similarity).
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Uniprot ID
PGH2_HUMAN
EC Number
EC: 1.14.99.1
Pfam
PF03098 ; PF00008
KEGG ID
hsa5743
TTD ID
T66665
INTEDE ID
DME0114
A List of Drug Combination(s) Able to Regulate This Molecule
          Activity Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Activity of This Molecule [1]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ferulic acid   NP Info  + Insulin   Drug Info 
                    Structure +
          Expression Regulation     Click to Show/Hide the Drug Combination Regulating This Molecule
                 Down-regulation     Click to Show/Hide
                    Drug Combination 1 Down-regulating the Expression of This Molecule [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 2 Down-regulating the Expression of This Molecule [3]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Wogonin   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 3 Down-regulating the Expression of This Molecule [4]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Silibinin   NP Info  + Indole-3-carbinol   Drug Info 
                    Structure +
                    Drug Combination 4 Down-regulating the Expression of This Molecule [5]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 5 Down-regulating the Expression of This Molecule [6]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gamma tocotrienol   NP Info  + GW9662   Drug Info 
                    Structure +
                    Drug Combination 6 Down-regulating the Expression of This Molecule [7]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 7 Down-regulating the Expression of This Molecule [8]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Plumbagin   NP Info  + Celecoxib   Drug Info 
                    Structure +
                    Drug Combination 8 Down-regulating the Expression of This Molecule [9]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Sulforaphane   NP Info  + Gefitinib   Drug Info 
                    Structure +
                    Drug Combination 9 Down-regulating the Expression of This Molecule [10]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name 6-shogaol   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 10 Down-regulating the Expression of This Molecule [11]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Celecoxib   Drug Info 
                    Structure +
                    Drug Combination 11 Down-regulating the Expression of This Molecule [12]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Celecoxib   Drug Info 
                    Structure +
                    Drug Combination 12 Down-regulating the Expression of This Molecule [13]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Chlorogenic acid   NP Info  + Methotrexate   Drug Info 
                    Structure +
                    Drug Combination 13 Down-regulating the Expression of This Molecule [14]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + 6-OH-11-O-Hydroxyphenanthrene   Drug Info 
                    Structure +
                    Drug Combination 14 Down-regulating the Expression of This Molecule [15]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Ursolic acid   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 15 Down-regulating the Expression of This Molecule [16]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Capecitabine   Drug Info 
                    Structure +
                    Drug Combination 16 Down-regulating the Expression of This Molecule [17]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Sulforaphane   NP Info  + Doxorubicin   Drug Info 
                    Structure +
                    Drug Combination 17 Down-regulating the Expression of This Molecule [18]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Eugenol   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 18 Down-regulating the Expression of This Molecule [19]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Dasatinib   Drug Info 
                    Structure +
                    Drug Combination 19 Down-regulating the Expression of This Molecule [20]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Alpha linolenic acid   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 20 Down-regulating the Expression of This Molecule [21]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Oroxylin A   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 21 Down-regulating the Expression of This Molecule [22]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 22 Down-regulating the Expression of This Molecule [23]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Resveratrol   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 23 Down-regulating the Expression of This Molecule [24]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Epigallocatechin gallate   NP Info  + Cisplatin   Drug Info 
                    Structure +
                    Drug Combination 24 Down-regulating the Expression of This Molecule [25]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Genistein   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 25 Down-regulating the Expression of This Molecule [26]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Gamma tocotrienol + Vitamin E + Celecoxib
    Click to Show/Hide the Each NP or Drug Structure of This Combination
Gamma tocotrienol   NP Info     Drug Info 
Vitamin E   NP Info 
                    Drug Combination 26 Down-regulating the Expression of This Molecule [27]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Shikonin   NP Info  + Gemcitabine   Drug Info 
                    Structure +
                    Drug Combination 27 Down-regulating the Expression of This Molecule [28]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Vitamin E   NP Info  + Aspirin   Drug Info 
                    Structure +
                    Drug Combination 28 Down-regulating the Expression of This Molecule [29]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Thymoquinone   NP Info  + 5-fluorouracil   Drug Info 
                    Structure +
                    Drug Combination 29 Down-regulating the Expression of This Molecule [30]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Alpha linolenic acid   NP Info  + Gentamicin   Drug Info 
                    Structure +
                    Drug Combination 30 Down-regulating the Expression of This Molecule [31]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Allyl isothiocyanate   NP Info  + Celecoxib   Drug Info 
                    Structure +
                    Drug Combination 31 Down-regulating the Expression of This Molecule [32]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Piperine   NP Info  + Celecoxib   Drug Info 
                    Structure +
                    Drug Combination 32 Down-regulating the Expression of This Molecule [33]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Nimustine hydrochloride   Drug Info 
                    Structure +
                    Drug Combination 33 Down-regulating the Expression of This Molecule [34]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Zerumbone   NP Info  + Nimesulide   Drug Info 
                    Structure +
                    Drug Combination 34 Down-regulating the Expression of This Molecule [35]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    Name Curcumin   NP Info  + Bacillus Calmette-Guerin   Drug Info 
                    Structure +
Natural Product(s) of This Target
1 Alpha linolenic acid  NP Info  Investigative Perilla frutescens
2 Alpha lipoic acid  NP Info  Investigative Spinacia oleracea
3 Cryptotanshinone  NP Info  Investigative Salvia miltiorrhiza
4 Isoliquiritigenin  NP Info  Investigative Robinia pseudoacacia
5 Meloxicam  NP Info  Approved Homo sapiens
6 Rofecoxib  NP Info  Approved Homo sapiens
7 Wogonin  NP Info  Investigative Scutellaria amoena
Drug(s) of This Target
1 Celecoxib  Drug Info  Approved Rheumatoid arthritis
2 Docosahexaenoic acid  Drug Info  Approved Hyper-lipoproteinaemia
3 Ibuprofen  Drug Info  Approved Pain
4 Indomethacin  Drug Info  Approved Rheumatoid arthritis
5 Loxoprofen  Drug Info  Phase 4 Ankylosing spondylitis
6 Naproxen  Drug Info  Approved Osteoarthritis
7 Nimesulide  Drug Info  Terminated Colorectal cancer
8 Nimustine hydrochloride  Drug Info  Phase 2 Brain cancer
References
Reference 1 Beneficial effects of ferulic acid alone and in combination with insulin in streptozotocin induced diabetic neuropathy in Sprague Dawley rats. Life Sci. 2020 Aug 15;255:117856.
Reference 2 Curcumin enhances cytotoxicity of chemotherapeutic agents in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappaB activation. Prostate. 2002 May 15;51(3):211-8.
Reference 3 Wogonin potentiates the antitumor effects of low dose 5-fluorouracil against gastric cancer through induction of apoptosis by down-regulation of NF-kappaB and regulation of its metabolism. Toxicol Lett. 2010 Sep 1;197(3):201-10.
Reference 4 Enhanced inhibition of lung adenocarcinoma by combinatorial treatment with indole-3-carbinol and silibinin in A/J mice. Carcinogenesis. 2011 Apr;32(4):561-7.
Reference 5 Effect of resveratrol and in combination with 5-FU on murine liver cancer. World J Gastroenterol. 2004 Oct 15;10(20):3048-52.
Reference 6 Synergistic Antiproliferative Effects of Combined Gamma -Tocotrienol and PPAR Gamma Antagonist Treatment Are Mediated through PPAR Gamma -Independent Mechanisms in Breast Cancer Cells. PPAR Res. 2014;2014:439146.
Reference 7 Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro. Cell Prolif. 2011 Dec;44(6):591-601.
Reference 8 Synergistic inhibitory effects of Celecoxib and Plumbagin on melanoma tumor growth. Cancer Lett. 2017 Jan 28;385:243-250.
Reference 9 Sulforaphane inhibits growth of human breast cancer cells and augments the therapeutic index of the chemotherapeutic drug, gemcitabine. Asian Pac J Cancer Prev. 2013;14(10):5855-60.
Reference 10 Antitumor activity of gemcitabine can be potentiated in pancreatic cancer through modulation of TLR4/NF-kappaB signaling by 6-shogaol. AAPS J. 2014 Mar;16(2):246-57.
Reference 11 Celecoxib and curcumin synergistically inhibit the growth of colorectal cancer cells. Clin Cancer Res. 2005 Sep 15;11(18):6738-44.
Reference 12 Resveratrol enhances the chemopreventive effect of celecoxib in chemically induced breast cancer in rats. Eur J Cancer Prev. 2014 Nov;23(6):506-13.
Reference 13 Protective effect of Chlorogenic acid against methotrexate induced oxidative stress, inflammation and apoptosis in rat liver: An experimental approach. Chem Biol Interact. 2017 Jun 25;272:80-91.
Reference 14 Epigallocatechin-3-gallate and 6-OH-11-O-Hydroxyphenanthrene Limit BE(2)-C Neuroblastoma Cell Growth and Neurosphere Formation In Vitro. Nutrients. 2018 Aug 22;10(9):1141.
Reference 15 Ursolic acid inhibits the growth of human pancreatic cancer and enhances the antitumor potential of gemcitabine in an orthotopic mouse model through suppression of the inflammatory microenvironment. Oncotarget. 2016 Mar 15;7(11):13182-96.
Reference 16 Curcumin sensitizes human colorectal cancer to capecitabine by modulation of cyclin D1, COX-2, MMP-9, VEGF and CXCR4 expression in an orthotopic mouse model. Int J Cancer. 2009 Nov 1;125(9):2187-97.
Reference 17 Sulforaphane increases the efficacy of doxorubicin in mouse fibroblasts characterized by p53 mutations. Mutat Res. 2006 Oct 10;601(1-2):92-101.
Reference 18 Eugenol enhances the chemotherapeutic potential of gemcitabine and induces anticarcinogenic and anti-inflammatory activity in human cervical cancer cells. Cancer Biother Radiopharm. 2011 Oct;26(5):519-27.
Reference 19 Curcumin enhances dasatinib-induced inhibition of growth and transformation of colon cancer cells. Int J Cancer. 2011 Feb 15;128(4):951-61.
Reference 20 Alpha-linolenic acid confers protection on mice renal cells against cisplatin-induced nephrotoxicity. Cytotechnology. 2019 Oct;71(5):905-914.
Reference 21 Synergistic effect of 5-fluorouracil and the flavanoid oroxylin A on HepG2 human hepatocellular carcinoma and on H22 transplanted mice. Cancer Chemother Pharmacol. 2010 Feb;65(3):481-9.
Reference 22 Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res. 2007 Apr 15;67(8):3853-61.
Reference 23 Resveratrol, a multitargeted agent, can enhance antitumor activity of gemcitabine in vitro and in orthotopic mouse model of human pancreatic cancer. Int J Cancer. 2010 Jul 15;127(2):257-68.
Reference 24 Reversal of Cisplatin resistance by epigallocatechin gallate is mediated by downregulation of axl and tyro 3 expression in human lung cancer cells. Korean J Physiol Pharmacol. 2014 Feb;18(1):61-6.
Reference 25 Combination of 5-fluorouracil and genistein induces apoptosis synergistically in chemo-resistant cancer cells through the modulation of AMPK and COX-2 signaling pathways. Biochem Biophys Res Commun. 2005 Jul 1;332(2):433-40.
Reference 26 Synergistic anticancer effects of combined gamma-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFkappaB signaling. Biomed Pharmacother. 2010 May;64(5):327-32.
Reference 27 Shikonin suppresses tumor growth and synergizes with gemcitabine in a pancreatic cancer xenograft model: Involvement of NF-kappaB signaling pathway. Biochem Pharmacol. 2014 Apr 1;88(3):322-33.
Reference 28 Synergistic inhibition of cyclooxygenase-2 expression by vitamin E and aspirin. Free Radic Biol Med. 2000 Dec;29(11):1135-42.
Reference 29 Thymoquinone subdues tumor growth and potentiates the chemopreventive effect of 5-fluorouracil on the early stages of colorectal carcinogenesis in rats. Drug Des Devel Ther. 2016 Jul 11;10:2239-53.
Reference 30 Protective effect of alpha-linolenic acid on gentamicin-induced ototoxicity in mice. Somatosens Mot Res. 2017 Sep;34(3):145-150.
Reference 31 Enhanced inhibition of urinary bladder cancer growth and muscle invasion by allyl isothiocyanate and celecoxib in combination. Carcinogenesis. 2013 Nov;34(11):2593-9.
Reference 32 Piperine and Celecoxib synergistically inhibit colon cancer cell proliferation via modulating Wnt/beta-catenin signaling pathway. Phytomedicine. 2021 Apr;84:153484.
Reference 33 Curcumin potentiates the potent antitumor activity of ACNU against glioblastoma by suppressing the PI3K/AKT and NF-kappaB/COX-2 signaling pathways. Onco Targets Ther. 2017 Nov 15;10:5471-5482.
Reference 34 Suppression of dextran sodium sulfate-induced colitis in mice by zerumbone, a subtropical ginger sesquiterpene, and nimesulide: separately and in combination. Biochem Pharmacol. 2003 Oct 1;66(7):1253-61.
Reference 35 Curcumin potentiates the antitumor effects of Bacillus Calmette-Guerin against bladder cancer through the downregulation of NF-kappaB and upregulation of TRAIL receptors. Cancer Res. 2009 Dec 1;69(23):8958-66.
Reference 36 Cox-2 inhibitory effects of naturally occurring and modified fatty acids. J Nat Prod. 2001 Jun;64(6):745-9.
Reference 37 Investigations concerning the COX/5-LOX inhibiting and hydroxyl radical scavenging potencies of novel 4,5-diaryl isoselenazoles. Eur J Med Chem. 2008 Jun;43(6):1152-9.
Reference 38 Cryptotanshinone Protects Cartilage against Developing Osteoarthritis through the miR-106a-5p/GLIS3 Axis. Mol Ther Nucleic Acids. 2018 Jun 1;11:170-179.
Reference 39 Inhibition of COX-2, mPGES-1 and CYP4A by isoliquiritigenin blocks the angiogenic Akt signaling in glioma through ceRNA effect of miR-194-5p and lncRNA NEAT1. J Exp Clin Cancer Res. 2019 Aug 22;38(1):371.
Reference 40 Meloxicam: selective COX-2 inhibition in clinical practice. Semin Arthritis Rheum. 1997 Jun;26(6 Suppl 1):21-7.
Reference 41 Privileged structures: a useful concept for the rational design of new lead drug candidates. Mini Rev Med Chem. 2007 Nov;7(11):1108-19.
Reference 42 Inhibitory activity of prostaglandin E2 production by the synthetic 2'-hydroxychalcone analogues: Synthesis and SAR study. Bioorg Med Chem Lett. 2009 Mar 15;19(6):1650-3.
Reference 43 Pfizer. Product Development Pipeline. March 31 2009.
Reference 44 Maternal toxicity of nonsteroidal anti-inflammatory drugs as an important factor affecting prenatal development. Reprod Toxicol. 2009 Sep;28(2):239-44.
Reference 45 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
Reference 46 Evaluation of loxoprofen and its alcohol metabolites for potency and selectivity of inhibition of cyclooxygenase-2. Bioorg Med Chem Lett. 2004 Mar 8;14(5):1201-3.
Reference 47 Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000 Oct;40(10):1109-20.
Reference 48 Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5.
Reference 49 Effects of migraine attack and metoclopramide on the absorption of tolfenamic acid. Br J Clin Pharmacol. 1984 Jan;17(1):67-75.
Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China