COX-2
Cyclooxygenase-2 (COX-2) is an inducible enzyme catalyzing the conversion of arachidonic acid to prostaglandin endoperoxides, central to prostanoid biosynthesis and inflammatory signaling[1][2]. Mechanistically, COX-2 activity is regulated by both its catalytic and allosteric subunits, allowing modulation by fatty acids and selective inhibitors, distinguishing it from constitutive COX-1[2]. COX-2 is strongly upregulated in response to pro-inflammatory cytokines, hypoxia, and tumor microenvironment signals, orchestrating prostaglandin E2 (PGE2) production and downstream activation of NF-κB and PI3K-Akt pathways[3][4][5]. In disease models, COX-2 contributes to cancer progression, atherosclerosis, and migraine through modulation of immune responses, vascular smooth muscle activity, and neuronal-glial interactions[6][7][5]. Compared with COX-1, COX-2 expression is more context-dependent and spatially regulated, being highly inducible in endothelial cells, arterial versus venous smooth muscle, and neuronal populations under stress or inflammatory stimuli[8][9][10]. Experimental studies demonstrate COX-2 as a critical mediator of ischemic preconditioning in the heart, providing cardioprotection via PGE2 and PGI2 signaling[11]. Selective COX-2 inhibitors, including synthetic NSAIDs and dual COX/LOX modulators, are utilized to interrogate COX-2 function and develop anti-inflammatory therapies with reduced gastrointestinal and cardiovascular side effects[3][12]. Agonist studies further highlight receptor-mediated induction of COX-2, exemplifying its role in colon carcinoma and trigeminal ganglia models[13][7].
References:
- [1]. Smith FG, et al. Cyclooxygenase (COX) Inhibitors and the Newborn Kidney. Pharmaceuticals (Basel). 2012 Oct 25;5(11):1160-76. [Content Brief]
- [2]. Ahmadi M, et al. Non-steroidal anti-inflammatory drugs: recent advances in the use of synthetic COX-2 inhibitors. RSC Med Chem. 2022 Feb 14;13(5):471-496. [Content Brief]
- [3]. Bolli R, et al. Discovery of a new function of cyclooxygenase (COX)-2: COX-2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning. Cardiovasc Res. 2002 Aug 15;55(3):506-19. [Content Brief]
- [4]. Kirkby NS, et al. COX-2 protects against atherosclerosis independently of local vascular prostacyclin: identification of COX-2 associated pathways implicate Rgl1 and lymphocyte networks. PLoS One. 2014 Jun 2;9(6):e98165. [Content Brief]
- [5]. Segelcke D, et al. The role of the spinal cyclooxygenase (COX) for incisional pain in rats at different developmental stages. Eur J Pain. 2020 Feb;24(2):312-324. [Content Brief]
- [6]. Chatzipieris FP, et al. Recent advances in dual COX/LOX inhibitor design (2020-2024). Life. 2026;16(1):163. [Content Brief]
- [7]. Yang WL, et al. Cholinergic receptor up-regulates COX-2 expression and prostaglandin E(2) production in colon cancer cells. Carcinogenesis. 2000 Oct;21(10):1789-93. [Content Brief]
- [8]. Hsieh HL, et al. c-Src-dependent EGF receptor transactivation contributes to ET-1-induced COX-2 expression in brain microvascular endothelial cells. J Neuroinflammation. 2012 Jul 2;9:152. [Content Brief]
- [9]. Neeb L, et al. IL-1β stimulates COX-2 dependent PGE₂ synthesis and CGRP release in rat trigeminal ganglia cells. PLoS One. 2011 Mar 4;6(3):e17360. [Content Brief]
- [10]. Chen S, et al. 288 The COX-2 pathway as a mediator of resistance to anti-PD-1 therapy. J Immunother Cancer. 2021;9(Suppl 2):A312.
- [11]. Bishop-Bailey D, et al. Differential induction of cyclooxygenase-2 in human arterial and venous smooth muscle: role of endogenous prostanoids. Arterioscler Thromb Vasc Biol. 1998 Oct;18(10):1655-61. [Content Brief]
- [12]. Majumder M, et al. COX-2 Elevates Oncogenic miR-526b in Breast Cancer by EP4 Activation. Mol Cancer Res. 2015 Jun;13(6):1022-33. [Content Brief]
- [13]. Scott KF, et al. Functional coupling and differential regulation of the phospholipase A2-cyclooxygenase pathways in inflammation. J Leukoc Biol. 1999 Oct;66(4):535-41. [Content Brief]
- [14]. Smith WL, et al. Interactions of fatty acids, nonsteroidal anti-inflammatory drugs, and coxibs with the catalytic and allosteric subunits of cyclooxygenases-1 and -2. J Biol Chem. 2019 Feb 1;294(5):1697-1705. [Content Brief]
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COX-2 Related Products (502)
Related Products (502)
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20(S)-Ginsenoside Rg3 (Standard)
0 ImagesSynonyms: 20(S)-Propanaxadiol(Standard); S-ginsenoside Rg3 (Standard)20(S)-Ginsenoside Rg3 (Standard) is the analytical standard of 20(S)-Ginsenoside Rg3. This product is intended for research and analytical applications. 20(S)-Ginsenoside Rg3 is the main component of Panax ginseng C. A. Meyer. Ginsenoside Rg3 inhibits Na+ and hKv1.4 channel with IC50s of 32.2±4.5 and 32.6±2.2 μM, respectively. 20(S)-Ginsenoside Rg3 also inhibits Aβ levels, NF-κB activity, and COX-2 expression.
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Anti-inflammatory agent 56
0 ImagesCat. No.: HY-155997CAS No.: 2413127-32-7Anti-inflammatory agent 56 (Compound 9) is a selective COX-2 inhibitor (IC50: 0.54 μM). Anti-inflammatory agent 56 has anti-oxidant and anti-inflammatory effects. Anti-inflammatory agent 56 inhibits oxidative stress induced cell death. Anti-inflammatory agent 56 inhibits oxidative stress and neuroinflammation by inhibiting Keap1, COX-2 and iNOS. Anti-inflammatory agent 56 has low acute toxicity in mice (LD50: 1000 mg/kg).
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Anti-inflammatory agent 112
0 ImagesCat. No.: HY-181156Anti-inflammatory agent 112 is an inducible nitric oxide synthase (iNOS) inhibitor, a COX-2 inhibitor, and an anti-inflammatory agent. Anti-inflammatory agent 112 suppresses i-NOS and COX-2 protein expression, reduces nitric oxide, IL-6, and TNF-α production, and attenuates lipopolysaccharide (LPS)-induced inflammatory responses. Anti-inflammatory agent 112 can be used for the research of inflammatory disorders.
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EGFR/COX-2-IN-2
0 ImagesCat. No.: HY-178440EGFR/COX-2-IN-2 (Compound 10a) is a dual inhibitor targeting epidermal growth factor receptor (EGFR) (IC50= 6.0 μM) and cyclooxygenase-2 (COX-2) (IC50=50 μM). EGFR/COX-2-IN-2 induces S-phase cell cycle arrest and apoptosis. EGFR/COX-2-IN-2 is promising for research of cancers and inflammation-related diseases.
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Leupeptin hemisulfate (Standard)
0 ImagesLeupeptin hemisulfate (Standard) is the analytical standard of Leupeptin hemisulfate (HY-18234A ). This product is intended for research and analytical applications. Leupeptin hemisulfate is a broad-spectrum protease inhibitor. By inhibiting the activation of the PTEN/PI3K/Akt/NF-κB/ERK1/2/p38 signaling pathway, Leupeptin hemisulfate significantly reduces LPS-induced NO and ROS production, mitochondrial membrane potential hyperpolarization, phagocytic activity, pro-inflammatory cytokine release, and M1 polarization in mouse peritoneal macrophages, and reverses autophagic flux impairment. It also decreases Concanavalin A (HY-P2149)-induced proliferation index of mouse splenic lymphocytes and the Th1/IL-10 and Th2/IL-10 cytokine ratios, thereby modulating innate and adaptive immune responses. Leupeptin hemisulfate inhibits blood coagulation and tumorigenesis in mouse skin. Leupeptin hemisulfate can be used in research on chronic inflammatory diseases and skin tumorigenesis.
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HDAC6-IN-71
0 ImagesCat. No.: HY-180829CAS No.: 3062867-16-4HDAC6-IN-71 (Compound 24) is a HDAC6 inhibitor with IC50 values for HDAC6 and HDAC1 of 13.68 and 443.12 nM respectively. HDAC6-IN-71 effectively inhibits the production of NO by mouse macrophages, with its IC50 being 2.31 μM. HDAC6-IN-71 inhibits the HDAC6-NF-κB signaling pathway, reduces the levels of phosphorylated IκB-α and IKK-α/β, and suppresses the expression of downstream inflammatory proteins COX-2 and iNOS. HDAC6-IN-71 significantly alleviates ulcerative colitis in mice.
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Triptolidenol
0 ImagesCat. No.: HY-N11784CAS No.: 99694-86-7Triptolidenol, a traditional Chinese medicine, is an epoxy diterpene lactone that can be isolated from Tripterygium wilfordii. Triptolidenol has anti-inflammatory and anticancer activities. Triptolidenol significantly inhibits tumor cell proliferation and migration, arrests cell cycle arrest at S phase and induces apoptosis by activating the cytochrome c/caspase cascade signaling pathway. Triptolidenol disrupts NF-κB/COX-2 pathway by inhibiting IKKβ at ATP-binding sites. Triptolidenol can be used for chronic nephritis and kidney cancer like clear cell renal cell carcinoma (ccRCC) research.
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15-LOX-IN-2
0 ImagesCat. No.: HY-17311515-LOX-IN-2 (Compound 2a) is an orally active COX-2/15-LOX inhibitor and a partial agonist of PPARγ. 15-LOX-IN-2 has anti-inflammatory activity and inhibits the levels of 20-HETE, IL-1β and TNF-α in RAW 264.7 cells treated with LPS (HY-D1056). In addition, 15-LOX-IN-2 has significant glucose uptake capacity in the absence of insulin. 15-LOX-IN-2 can be used for the research of metabolic diseases.
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COX-2-IN-61
0 ImagesCat. No.: HY-179700COX-2-IN-61 is an orally active COX-2 inhibitor with an IC50 of 22 µM, also inhibits COX-1 with an IC50 of 43 µM. COX-2-IN-61 exhibits anti-inflammation effects in a Carrageenan (HY-125474) induced rat paw edema model, with promising safety profiles. COX-2-IN-61 can be used for the research of inflammation.
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Dihydroflavokawin B
0 ImagesCat. No.: HY-W676872CAS No.: 3791-76-2Dihydroflavokawin B is a selective COX-1 inhibitor with an IC50 of 1.22 μM. Dihydroflavokawin B weakly inhibits COX-2 and 5-LOX. Dihydroflavokawin B inhibits promastigote forms of Leishmania panamensis and Leishmania braziliensis. Dihydroflavokawin B inhibits rabbit platelet aggregation induced by Arachidonic acid, platelet activating factor, and adenosine diphosphate. Dihydroflavokawin B exhibits in vitro anti-inflammatory activity. Dihydroflavokawin B can be used for the research of leishmaniasis.
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(±)-Methotrexate-d3
0 ImagesCat. No.: HY-121151SSynonyms: (±)-Amethopterin-d3; (±)-CL14377-d3; (±)-WR19039-d3(±)-Methotrexate-d3 ((±)-Amethopterin-d3; (±)-CL14377-d3; (±)-WR19039-d3) is the deuterated-labeled (±)-Methotrexate (HY-121151). (±)-Methotrexate is the racemate of Methotrexate (HY-14519). Methotrexate is an orally active antifolate (Antifolate). Methotrexate inhibits dihydrofolate reductase (DHFR), blocks tetrahydrofolate production, suppresses purine/pyrimidine synthesis and transmethylation, and causes intracellular accumulation of AICAR. Methotrexate promotes extracellular adenosine release, regulates the cytokine network, and inhibits the alarmin function of HMGB1. Methotrexate induces apoptosis and cytotoxicity, upregulates the expression of iNOS and COX-2, suppresses hippocampal neurogenesis, and induces pulmonary fibrosis. Methotrexate is used in the research of various immune and inflammation-related diseases such as arthritis, psoriasis, systemic lupus erythematosus, as well as pulmonary fibrosis and breast cancer.
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NF-κB/STAT3/iNOS-IN-1
0 ImagesCat. No.: HY-184692NF-κB/STAT3/iNOS-IN-1 is a NF-κB/STAT3/iNOS inhibitor. NF-κB/STAT3/iNOS-IN-1 reduces the expression of inflammatory mediators TNF-α, IL-1β, IL-6, IL-8 and COX-2. NF-κB/STAT3/iNOS-IN-1 upregulates the expression of epithelial barrier-related proteins E-cadherin, Occludin and Zonula occludens-1. NF-κB/STAT3/iNOS-IN-1 alleviates disease severity and histopathological damage in mouse colitis models. NF-κB/STAT3/iNOS-IN-1 can be used for the research of inflammatory bowel disease (colitis).
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Eltenac
0 ImagesCat. No.: HY-106093CAS No.: 72895-88-6Eltenac, a non-steroidal anti-inflammatory drug (NSAID), is a COX inhibitor. Eltenac shows IC50 of 0.03 μM for both COX-1 and COX-2 in isolated human whole blood.
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Multi-kinase-IN-8
0 ImagesCat. No.: HY-179439Multi-kinase-IN-8 is a muti-kinase inhibitor. Multi-kinase-IN-8 inhibits COX-1 (IC50 of 12.6 μM), COX-2 (IC50 of 0.05 μM) and VEGFR-2 (IC50 of 0.12 nM). Multi-kinase-IN-8 inhibits tumor-associated carbonic anhydrases (CA IX and CA XII with Ki of 31.5 nM and 386.9 nM, respectively). Multi-kinase-IN-8 triggers cell cycle arrest and apoptosis through upregulation of Caspase 9 and Bax along with downregulation of Bcl 2. Multi-kinase-IN-8 suppresses PGE2, p-VEGFR-2, MMP-9 and HIF-1α and exhibits growth-inhibitory activity against breast cancer, lung cancer, and colorectal adenocarcinoma.
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(±)-Methotrexate
0 ImagesCat. No.: HY-121151CAS No.: 60388-53-6Synonyms: (±)-Amethopterin; (±)-CL14377; (±)-WR19039(±)-Methotrexate ((±)-Amethopterin; (±)-CL14377; (±)-WR19039) is the racemate of Methotrexate (HY-14519). Methotrexate is an orally active antifolate (Antifolate). Methotrexate inhibits dihydrofolate reductase (DHFR), blocks tetrahydrofolate production, suppresses purine/pyrimidine synthesis and transmethylation, and causes intracellular accumulation of AICAR. Methotrexate promotes extracellular adenosine release, regulates the cytokine network, and inhibits the alarmin function of HMGB1. Methotrexate induces apoptosis and cytotoxicity, upregulates the expression of iNOS and COX-2, suppresses hippocampal neurogenesis, and induces pulmonary fibrosis. Methotrexate is used in the research of various immune and inflammation-related diseases such as arthritis, psoriasis, systemic lupus erythematosus, as well as pulmonary fibrosis and breast cancer.
