COX-2 Inhibitor

Oleocanthal is an orally active phenolic seciridoid compound. Oleocanthal can be extracted from olive oil. Oleocanthal inhibits COX-1 and COX-2, reduces ROS and NO, and upregulates Nrf-2 and HO-1. Oleocanthal reduces Aβ deposition. Oleocanthal exhibits anti-Leishmania activity against promastigotes and amastigotes of L. major, with IC₅₀ values of 18.7 and 87 μg/mL, respectively. Oleocanthal exhibits anticancer activity against colon, breast, liver, and melanoma cancers. Oleocanthal also exhibits anti-inflammatory and neuroprotective properties. Oleocanthal can be used in Alzheimer's disease research.

4,4'-Dihydroxy-2,6-dimethoxydihydrochalcone exhibits COX-1 and COX-2 inhibitory activity.

Wnt/β-catenin-IN-6 is an orally active Wnt/β-catenin pathway inhibitor. Wnt/β-catenin-IN-6 blocks the AKT/GSK-3β/β-catenin signaling pathway, leading to reduced expression of Wnt target genes (c-Myc, c-Jun). Wnt/β-catenin-IN-6 reduces COX2 expression and IL-8 levels, highlighting its dual anti-inflammatory and antitumor effects. Wnt/β-catenin-IN-6 can induce apoptosis. Wnt/β-catenin-IN-6 serves as a tool for non-small cell lung cancer (NSCLC) research.

2,2'-Biphenol (o,o'-Biphenol) is an anti-inflammatory agent and the major non-protein-bound phenolic metabolite activated by rat bone marrow homogenate and hydrogen peroxide. 2,2'-Biphenol inhibits lipopolysaccharide (LPS) (HY-D1056)-induced COX-2 mRNA and protein expression. 2,2'-Biphenol suppresses the binding of AP-1 and NF-κB to their respective consensus sequences. 2,2'-Biphenol is applicable to research related to inflammation.

Enflicoxib (E 6087) is a nonsteroidal anti-inflammatory compound that selectively inhibits cyclooxygenase-2 (COX-2).?Enflicoxib does not inhibit cyclooxygenase-1 (COX-1). E-6087 shows anti-inflammatory, analgesic and antipyretic activities in animal models.

trans-Isoferulic acid (trans-3-Hydroxy-4-methoxycinnamic acid) is an aromatic acid that exhibits anti-inflammatory activity. trans-Isoferulic acid dephosphorylates PI3K/Akt, suppresses LPS (HY-D1056)-induced NF-κB activation, enhances Nrf2 activity, downregulates iNOS and COX-2 expression, induces HO-1 expression, inhibits NO and PGE₂ production, and scavenges hydroperoxyl radical. trans-Isoferulic acid can be used for research of inflammatiory diseases.

Plantanone B is a moderate antioxidant-agent with an IC₅₀ of 169.8±5.2 μM. Plantanone B shows significant ovine COX-1 and moderate COX-2 inhibitory activities. Plantanone B has the potential for inflammation-related diseases research.

Hordenine hydrochloride (Ordenina hydrochloride; Peyocactine hydrochloride) is a multifunctional alkaloid with oral activity and blood-brain barrier penetration. Hordenine hydrochloride inhibits LPS-induced phosphorylation of p38, JNK, ERK1/2, p65, IκB, and AKT, prevents p65 nuclear translocation, and suppresses inflammatory cytokines and mediators. Hordenine hydrochloride promotes M2 macrophage polarization, restores blood-milk barrier integrity, alleviates oxidative stress by reducing ROS and MDA, and attenuates LPS-induced lung injury and pulmonary edema. Hordenine hydrochloride inhibits cAMP production, CREB phosphorylation, and MITF expression, thereby suppressing melanin synthesis in melanocytes and reconstructed epidermis. Hordenine hydrochloride activates the Wnt/β-catenin signaling pathway, promotes dermal papilla cell proliferation and hair shaft elongation, and accelerates hair regeneration. Hordenine hydrochloride activates DRD2, acts as a D3R partial agonist, α2A-AR full agonist, and 5-HT2A-R antagonist, and inhibits SERT and DAT. Hordenine hydrochloride inhibits α-synuclein accumulation and ameliorates motor deficits in Parkinson's disease models. Hordenine hydrochloride limits alcohol intake, reduces relapse drinking behavior, and modulates alcohol-induced conditioned place preference. Hordenine hydrochloride can be used for research on mastitis, skin pigmentation, acute lung injury, foodborne diseases, hair loss, Parkinson's disease, bacterial infections, and alcohol use disorder.

Tolmetin sodium dihydrate is an orally active and potent COX inhibitor with IC₅₀s of 0.35 μM and 0.82 μM human COX-1 and COX-2, respectively. Tolmetin sodium dihydrate is a non-steroidal anti-inflammatory drug (NSAID).

Polmacoxib (CG100649) is a first-in-class, orally active nonsteroidal anti-inflammatory agent (NSAID) which is a dual inhibitor of COX-2 (IC₅₀ around 0.1 μg/ml) and carbonic anhydrase. Polmacoxib inhibits colorectal adenoma and tumor growth in mouse models.

Phellodendrine is an orally active plant alkaloid. Phellodendrine inhibits the proliferation of KRAS-mutated pancreatic cancer cells by suppressing macropinocytosis and glutamine metabolism, inducing ROS accumulation and mitochondrial apoptosis. Phellodendrine promotes autophagy by activating the AMPK/mTOR pathway, alleviating intestinal damage in ulcerative colitis. Phellodendrine can alleviate gouty arthritis by inhibiting the IL-6/STAT3 signaling pathway. Phellodendrine suppresses allergic reactions by altering the conformation of MRGPRB3/MRGPRX2 protein, thereby inhibiting the activation of PKC and subsequent downstream MAPK and NF-κB signaling. Phellodendrine inhibits the AKT/NF-κB pathway and down-regulates the expression of COX-2, thereby protecting zebrafish embryos from oxidative stress. Phellodendrine has an anti-major depressive disorder (MDD) effect by down-regulating CHRM1, HTR1A, and the PI3K/Akt signaling pathway.

Dipyrocetyl is a Salicylic Acid (HY-B0167) derivative, exhibiting analgesic and antipyretic activity. Dipyrocetyl can be used for inflammation diseases and pain.

Desmethyl Celecoxib (compound 3b) is a selective cyclooxygenase-2 (COX-2) inhibitor (IC₅₀=32 nM) with anti-inflammatory activities. Desmethyl Celecoxib is an analog of Celecoxib and with the optimal yield of 75%.

Shizukaol B is a lindenane-type dimeric sesquiterpene, used to be isolated from the whole plant of Chloranthus henryi. Shizukaol B has anti-inflammatory effect against lipopolysaccharide (LPS)-induced activation of BV2 microglial cells. Shizukaol B inhibits iNOS and COX-2, and suppresses NO production, TNF-α, and IL-1β expression.