COX-2 Inhibitor

Niflumic acid is a calcium-activated chloride channel blocker and COX-2 inhibitor with the IC₅₀ value of 100 nM. Niflumic acid induces apoptosis through caspase-8/Bid/Bax pathway in lung cancer cells. Niflumic acide exhibits anti-tumor activity by affecting the expression of ERK1/2 and the activity of MMP2 and MMP9. Niflumic acid has orally bioactivity. Niflumic acid acts on rheumatoid arthritis.

Guaiacol, a phenolic compound, inhibits LPS-stimulated COX-2 expression and NF-κB activation. Anti-inflammatory activity.

Madecassic acid is isolated from Centella asiatica (Umbelliferae). Madecassic acid has anti-inflammatory properties caused by iNOS, COX-2, TNF-alpha, IL-1beta, and IL-6 inhibition via the downregulation of NF-κB activation in RAW 264.7 macrophage cells.

Ginsenoside Rd inhibits TNFα-induced NF-κB transcriptional activity with an IC₅₀ of 12.05±0.82 μM in HepG2 cells. Ginsenoside Rd inhibits expression of COX-2 and iNOS mRNA. Ginsenoside Rd also inhibits Ca²⁺ influx. Ginsenoside Rd inhibits CYP2D6, CYP1A2, CYP3A4, and CYP2C9, with IC₅₀s of 58.0±4.5 μM, 78.4±5.3 μM, 81.7±2.6 μM, and 85.1±9.1 μM, respectively.

Rofecoxib is a potent, specific and orally active COX-2 inhibitor, with IC₅₀s of 26 and 18 nM for human COX-2 in human osteosarcoma cells and Chinese hamster ovary cells, with a 1000-fold selectivity for COX-2 over human COX-1 (IC₅₀ > 50 μM in U937 cells and > 15 μM in Chinese hamster ovary cells).

Nimesulide is a selective COX-2 inhibitor, with IC₅₀s of 70 nM-70 μM in a time-dependent manner, but it shows no effect on COX-1 (IC₅₀ >100 μM). Nimesulide has potent anti-inflammatory, analgesic and antipyretic properties.

Terameprocol is an inhibitor targeting the Sp1 transcription factor, which can selectively inhibit the transcription of Sp1-dependent genes. Terameprocol exerts its effects by inhibiting Sp1-mediated gene transcription, such as reducing the expression of genes like CDC2, survivin and HMGB1, thereby arresting the cell cycle, inducing apoptosis, and suppressing the inflammatory response. Terameprocol exhibits anti-proliferative, pro-apoptotic, and anti-inflammatory activities and is currently mainly used in the research of diseases such as cancer and pulmonary arterial hypertension[1][2][3].

Sodium thiosulfate (Sodium hyposulfite) is an antioxidant. Sodium thiosulfate inhibits the expression of p-GSK-3β and β-catenin proteins, reduces IL-1β, COX-2, and Iba-1, and inhibits NFκB activation. Sodium thiosulfate promotes angiogenesis, inhibits inflammation, and improves acute lung injury. Sodium thiosulfate also exhibits anti-cancer activity against melanoma. Sodium thiosulfate also exerts renal protective effects. Sodium thiosulfate can be used in the research of osteoarthritis, brain inflammation, cancer (such as breast cancer, melanoma), and kidney disease.

Oxaprozin is an orally active and potent COX inhibitor, with IC₅₀ values of 2.2 μM for human platelet COX-1 and and 36 μM for IL-1-stimulated human synovial cell COX-2, respectively. Oxaprozin also inhibits the activation of NF-κB. Oxaprozin induces cell apoptosis. Oxaprozin shows anti-inflammatory activity. Oxaprozin-mediated inhibition of the Akt/IKK/NF-κB pathway contributes to its anti-inflammatory properties.

Fenofibric acid, an active metabolite of fenofibrate, is a PPAR activitor, with EC₅₀s of 22.4 μM, 1.47 μM, and 1.06 μM for PPARα, PPARγ and PPARδ, respectively; Fenofibric acid also inhibits COX-2 enzyme activity, with an IC₅₀ of 48 nM.

STAT1/3-IN-1 is a potent STAT1/3 inhibitor with potent anti-inflammatory effect. STAT1/3-IN-1 inhibits phosphorylation and nuclear translocation of STAT1/3 to modulate microglial inflammation, reduces LPS (HY-D1056)-induced pro-inflammatory cytokines (NO, IL-1β, IL-6, and TNF-α) and inflammatory mediators (iNOS, COX-2). STAT1/3-IN-1 exhibits low toxicity in mice. STAT1/3-IN-1 can be used for the research of neuroinflammation.

Naproxen sodium is a COX-1 and COX-2 inhibitor with IC₅₀s of 8.72 and 5.15 μM, respectively in cell assay.

Psoralidin is a dual inhibitor of COX-2 and 5-LOX, regulates ionizing radiation (IR)-induced pulmonary inflammation.Anti-cancer, anti-bacterial, and anti-inflammatory properties. Psoralidin significantly downregulates NOTCH1 signaling. Psoralidin also greatly induces ROS generation.

Isofraxidin, a coumarin component from Acanthopanax senticosus, inhibits MMP-7 expression and cell invasion of human hepatoma cells. Isofraxidin inhibits the phosphorylation of ERK1/2 in hepatoma cells. Isofraxidin attenuates the expression of iNOS and COX-2, Isofraxidinalso inhibits TLR4/myeloid differentiation protein-2 (MD-2) complex formation.

Gamma-Mangostin is a novel competitive 5-hydroxytryptamine 2A (5-HT2A) receptor antagonist and potent epoxidase 2 (COX-2) inhibitor, as well as a transthyroxin protein (TTR) profibrosis inhibitor. Gamma-Mangostin binds to the thyroxine (T4)-binding sites and stabilized the TTR tetramer. Gamma-Mangostin inhibits [3^H] spiperone binding to cultured rat aortic myocytes (IC₅₀=3.5 nM) and reduces The perfusion pressure response of rat coronary artery to 5-HT2A (IC₅₀=0.32 μM). Gamma-Mangostin has anti-inflammatory, antibacterial, antioxidant and anticancer activities, and can be used in the study of metabolic disorders such as diabetes.

Ethyl Caffeate is a natural phenolic compound isolated from Bidens pilosa. Ethyl caffeate suppresses NF-κB activation and its downstream inflammatory mediators, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and prostaglandin E₂ (PGE₂) in vitro or in mouse skin.

Methotrexate hydrate (Amethopterin hydrate; CL14377 hydrate; WR19039 hydrate) is an orally active antifolate (Antifolate). Methotrexate hydrate inhibits dihydrofolate reductase (DHFR), blocks tetrahydrofolate production, suppresses purine/pyrimidine synthesis and transmethylation, and causes intracellular accumulation of AICAR. Methotrexate hydrate promotes extracellular adenosine release, regulates the cytokine network, and inhibits the alarmin function of HMGB1. Methotrexate hydrate induces apoptosis and cytotoxicity, upregulates the expression of iNOS and COX-2, suppresses hippocampal neurogenesis, and induces pulmonary fibrosis. Methotrexate hydrate 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.

S-(+)-Marmesin is a natural coumarin, exhibiting COX-2/5-LOX dual inhibitory activity.

Syringaldehyde is a polyphenolic compound belonging to the group of flavonoids and is found in different plant species like Manihot esculenta and Magnolia officinalis. Syringaldehyde moderately inhibits COX-2 activity with an IC₅₀ of 3.5 μg/mL. Anti-hyperglycemic and anti-inflammatory activities.