Lipoxygenase Inhibitor

U-73122 is a phospholipase C (PLC) and 5-LO (5-lipoxygenase) inhibitor with an IC₅₀of 1-2.1 µM for PLC.

Zileuton is a potent and selective inhibitor of 5-lipoxygenase with antiasthmatic properties.

Caffeic acid is an inhibitor of both TRPV1 ion channel and 5-Lipoxygenase (5-LO).

Nordihydroguaiaretic acid is a 5-lipoxygenase (5LOX) (IC₅₀=8 μM) and tyrosine kinase inhibitor.

CGS 23885 is an orally active 5-lipoxygenase (5-lipoxygenase) inhibitor. CGS 23885 reduces the production of 5-hydroxyeicosatetraenoic acid (5-hydroxyeicosatetraenoic acid), LTB₄, and LTC₄/D₄/E₄. CGS 23885 inhibits cell infiltration in rat pleurisy. CGS 23885 can be used in pleurisy-related research.

COX-2/5-LOX-IN-8 is an orally active dual COX-2/5-LOX inhibitor, with an IC₅₀ of 6.30 μM against sheep-derived COX-2 and an IC₅₀ of 8.09 μM against 5-LOX. COX-2/5-LOX-IN-8 acts as a membrane stabilizer that stabilizes erythrocyte membranes against hypotonicity-induced hemolysis. COX-2/5-LOX-IN-8 functions as a protein stabilizer that inhibits heat-induced denaturation of bovine serum albumin. COX-2/5-LOX-IN-8 reduces paw swelling, improves hind limb weight-bearing function, decreases serum levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, CRP), and lowers serum levels of cartilage degradation biomarkers (COMP, MMP-3, CTX-II). COX-2/5-LOX-IN-8 can be used in the research of osteoarthritis.

Buddledin A is a 5-LOX inhibitor (IC₅₀ = 50.4 μM) and a COX inhibitor (IC₅₀ = 13.7 μM). Buddedin A inhibits arachidonic acid metabolism via the 5-LOX and COX pathways, suppresses fungal growth, and exerts toxic effects on fish. Buddedin A may play an ecological role in protecting plant roots and stem barks from fungal infection. Buddedin A can be used in studies related to fungal infections.

ML355 is a potent and selective inhibitor of 12-Lipoxygenase (12-LOX) with an IC₅₀ of 0.34 μM, shows excellent selectivity over related lipoxygenases and cyclooxygenases, and possesses favorable ADME properties.

Wedelolactone suppresses LPS-induced caspase-11 expression by directly inhibits the IKK Complex. Wedelolactone also inhibits 5-lipoxygenase (5-Lox) with an IC₅₀ of 2.5 μM. Wedelolactone induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKCε without inhibiting Akt. Wedelolactone can extract from Eclipta alba, and it can be used for the research of cancer.

ML351 is a potent and highly specific 15-LOX-1 inhibitor with an IC₅₀ of 200 nM. ML351 shows excellent selectivity (>250-fold) versus the related isozymes, 5-LOX, platelet 12-LOX, 15-LOX-2, ovine COX-1, and human COX-2. ML351 prevents dysglycemia and reduces β-cell oxidative stress in nonobese diabetic mouse model of T1D.

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.

Masoprocol (meso-Nordihydroguaiaretic acid) is a potent and orally active lipoxygenase inhibitor. Masoprocol shows antihyperglycemic activity. Masoprocol decreases the glucose concentration and hepatic triglyceride in vivo. Masoprocol has the potential for the research of type II diabetes.

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

N-Oleoyldopamine (OLDA) is an orally active TRPV1 activator and 5-LOX inhibitor with blood-brain barrier permeability. N-Oleoyldopamine excites histaminergic neurons in the tuberomammillary nucleus via a dopamine receptor mechanism, a process independent of TRPV1 and cannabinoid receptors. On one hand, N-Oleoyldopamine promotes the release of insulin and glucose-dependent insulinotropic polypeptide through a GPR119-dependent pathway to improve glucose tolerance; on the other hand, N-Oleoyldopamine improves left ventricular function and reduces myocardial infarction size by triggering the release of substance P and calcitonin gene-related peptide. N-Oleoyldopamine is used in studies related to glycemic abnormalities and myocardial ischemia-reperfusion injury.

Chebulagic acid is a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz, on angiogenesis. Chebulagic acid is a M2 serine to asparagine 31 mutation (S31N) inhibitor and influenza antiviral. Chebulagic acid also against SARS-CoV-2 viral replication with an EC₅₀ of 9.76 μM.

Pectolinarigenin is an orally active dual inhibitor of COX-2/5-LOX with anti-inflammatory, antioxidant, antitumor and neuroprotective activities. Pectolinarigenin exerts neuroprotective and anti-inflammatory effects on astrocyte inflammation via the NFκB and MAPK pathways. Pectolinarigenin inhibits LPS-induced phosphorylation of ERK1/2, N-FκB and p38MAPK, directly inhibits the enzymatic activity or binding of COX-2, 5-LOX and HIF-1α, and reduces the level of XIAP. Pectolinarigenin modifies Keap1 to promote nuclear accumulation of Nrf2, induces ARE-mediated antioxidant enzyme expression, and possesses direct free radical scavenging activity. Pectolinarigenin reduces the release of NO, proinflammatory mediators and leukotrienes, and increases the level of IL-10. Pectolinarigenin induces G₂/M cell cycle arrest, apoptosis (Apoptosis) and autophagy (Autophagy) via the PI3K/AKT/mTOR signaling pathway. Pectolinarigenin reduces renal crystal deposition and inhibits melanin synthesis. Pectolinarigenin inhibits inflammation and alleviates allergy in mouse models of inflammation. Pectolinarigenin alleviates renal injury, inflammation and oxidative stress in mice by inhibiting HIF-1α activity. Pectolinarigenin can be used for the research of neurodegenerative diseases, inflammatory/allergic diseases, calcium oxalate nephrocalcinosis, gastric cancer, melasma, post-inflammatory diseases and chloasma.

Indirubin-3'-monoxime is a potent GSK-3β inhibitor, and weakly inhibits 5-Lipoxygenase, with IC₅₀s of 22 nM and 7.8-10 µM, respectively; Indirubin-3'-monoxime also shows inhibitory activities against CDK5/p25 and CDK1/cyclin B, with IC₅₀s of 100 and 180 nM.

Malotilate (NKK 105), an orally active hepatotropic agent and an anti-fibrotic substance, selectively inhibits the 5-lipoxygenase (5-LOX) (IC₅₀=4.7 μM). Malotilate prevents the development of hepatocytic injury in alcohol-pyrazole hepatitis by decreasing hepatic acetaldehyde levels and preventing the retention of transferrin in the hepatocytes.

Licofelone (ML-3000) is a dual COX/5-lipoxygenase (5-LOX) inhibitor (IC₅₀=0.21/0.18 μM, respectively) for the treatment of osteoarthritis. Licofelone exerts anti-inflammatory and anti-proliferative effects. Licofelone induces apoptosis, and decreases the production of proinflammatory leukotrienes and prostaglandins.

MK-0731 is a selective, non-competitive and allosteric kinesin spindle protein (KSP) inhibitor with an IC₅₀ of 2.2 nM and a pK_a of 7.6. MK-0731 is >20,000 fold selectivity against other kinesins. MK-0731 induces mitotic arrest and induces apoptosis in tumors. MK-0731 provides significant antitumor efficacy.