Lipoxygenase Inhibitor

PF-4191834 (PF-04191834) is an orally active, noniron chelating, and non-redox inhibitor of the 5-Lipoxygenase (5-LOX) (IC₅₀=229 nM), displays ~300-fold selectivity for 5-LOX over 12-LOX and 15-LOX, shows no activity toward the cyclooxygenase enzymes, and is effective in inflammation and pain.

3-Aminobutanoic acid is a β-amino acid. 3-Aminobutanoic acid can protect plant against a challenge infection with P. infestans. 3-Aminobutanoic acid has various levels of susceptibility for the pathogen.

Mirificin (Puerarin apioside) is a blood-brain barrier-permeable tyrosinase inhibitor, with an IC₅₀ value of 12.66 μM against mushroom tyrosinase. Mirificin reduces the expression of ALOX12 in cardiomyocytes and alleviates hypoxia/reoxygenation-induced apoptosis. The neuroprotective effect of Mirificin depends on the activation of VEGFR2 and HSP1A1, which reduces cerebral infarct size and improves neurological function. Mirificin can be used in the research of hyperpigmentation, acute myocardial infarction and ischemic stroke.

Phenethyl ferulate is a major constituent ofQianghuo, shows inhibitory activity against cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) with IC₅₀ values of 4.35 μM and 5.75 μM, respectively.

3',4'-Dihydroxyflavone is an orally active antioxidant. 3',4'-Dihydroxyflavone inhibits the NF-κB, JAK1/STAT1, AP-1, IRF3, and MAPK/MEK/ERK pathways, while activating Nrf2 and reducing Keap1, thereby exerting anti-inflammatory and antioxidant effects. 3',4'-Dihydroxyflavone inhibits NO, PGE₂, pro-inflammatory cytokines, and ROS production, upregulates GSH, and activates K_ATP channels, adenosine A₃ receptors, and GABA_A receptors. 3',4'-Dihydroxyflavone inhibits PPARγ expression and adipogenic differentiation, induces osteogenic differentiation; it also inhibits 5-lipoxygenase and xanthine oxidase, weakly inhibits PARP1, and scavenges DPPH and superoxide radicals. 3',4'-Dihydroxyflavone can be used for research on peripheral nerve injury, septic shock, obesity, influenza A virus infection, infertility, and diabetic complications.

Docebenone (AA 861) is a potent, selective and orally active 5-LO (5-lipoxygenase) inhibitor.

Timosaponin A1, a natural steroidal saponin, is a 5-lipoxygenase (5-LO), COX-2, and dipeptidyl peptidase 4 (DPP-4) inhibitor with IC₅₀s of 3.29 µM, 36.43 µM, and 33.25 µM, respectively.

Utreloxastat (PTC857) is an orally active and blood-brain barrier-permeable 15-lipooxygenase inhibitor. Utreloxastat is a weak inhibitor of CYP1A2 and 2B6 with an IC₅₀ of >5.3 μM. Utreloxastat reduces oxidative stress and inhibits the consumption of reduced glutathione and ferroptosis. Utreloxastat can be used in the study of neurodegenerative diseases characterized by high levels of oxidative stress and mitochondrial pathology, such as amyotrophic lateral sclerosisc.

5-O-Demethylnobiletin (5-Demethylnobiletin), a polymethoxyflavone isolated from Citrus jambhiri Lush., is a direct inhibition of 5-LOX (IC₅₀=0.1 μM), without affecting the expression of COX-2. 5-O-Demethylnobiletin (5-Demethylnobiletin) has anti-inflammatory activity, inhibits leukotriene B (4)(LTB₄) formation in rat neutrophils and elastase release in human neutrophils with an IC₅₀ of 0.35 μM.

Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC) is a potent 12/15-Lipoxygenases (LO) inhibitor. Cinnamyl-3,4-dihydroxy-α-cyanocinnamate has the potential for the research of type 1 diabetes mellitus.

Eicosatetraynoic acid (ETYA) is a non-metabolizable analog of Arachidonic acid (HY-109590) and also an inhibitor of the lipoxygenase (LOX)/cyclooxygenase (COX) pathway (ID₅₀ = 8 μM and 4 μM). Eicosatetraynoic acid acts as a suicide substrate to inhibit the production of inflammatory mediators such as leukotrienes and prostaglandins. Eicosatetraynoic acid acts directly on cell membranes and membrane proteins to exert a wide range of effects, including blocking potassium channels, increasing cell membrane fluidity, elevating intracellular calcium levels, inhibiting DNA synthesis in tumor cells, inducing differentiation of certain cells, and specifically inhibiting the assembly and replication of orthopoxviruses. Eicosatetraynoic acid alleviates acute lung injury induced by chemicals such as phosgene.

CJ-13,610, a nonredox-type 5-LO inhibitor, dose dependently suppresses 5-LO product formation in ionophore A23187-stimulated PMNL in the absence of exogenous AA with an IC₅₀ of about 70 nM. PMNL: polymorphonuclear leukocytes; AA: arachidonic acid

FPL 62064 is a potent 5-lipoxygenase (5-LOX) and COX dual inhibitor, with IC₅₀ values of 3.5 μM and 3.1 μM for RBL-1 cytosolic 5-lipoxygenase and prostaglandin synthetase (cyclooxygenase), respectively. FPL 62064 has potent anti-inflammatory activity.

3-Hydroxy-2-pyrone (Compound 12d) is a metalloenzyme inhibitor. 3-Hydroxy-2-pyrone shows an inhibition rate of approximately 50% for matrix metalloproteinases (MMP) and the inhibition rate for non-heme iron enzyme 5-lipoxygenase (5-LOX) was over 70% at 1 mM. 3-Hydroxy-2-pyrone also has certain inhibitory activity against copper-dependent enzyme tyrosinase. 3-Hydroxy-2-pyrone can be used for the research of cancer, infection and inflammation.

ThioLox is a competitive 15-lipoxygenase-1 (15-LOX-1) inhibitor with a K_i of 3.30 μM. ThioLox shows anti-inflammatory and neuroprotective properties.

7,3',4'-Tri-O-methylluteolin (5-Hydroxy-3',4',7-trimethoxyflavone) is a flavonoid with multiple biological activities. 7,3',4'-Tri-O-methylluteolin inhibits soybean lipoxygenase (LOX), with an IC₅₀ value of 23.97 µg/mL. 7,3',4'-Tri-O-methylluteolin possesses anti-inflammatory effects in Lipopolysaccharides (HY-D1056) (LPS)-induced RAW 264.7 macrophages. 7,3',4'-Tri-O-methylluteolin inhibits the binding of MDM2 with p53 and induces apoptosis in MCF-7 breast cancer cells. 7,3',4'-Tri-O-methylluteolin also has antioxidant, antifungal and antitrypanosomal activities.

Methyl orsellinate acts as an antiviral agent and insecticide. Methyl orsellinate exhibits enzyme inhibitory activity, with an IC₅₀ of 59.6 µM against porcine leukocyte 5-lipoxygenase (5-LOX); it inhibits soybean 15-lipoxygenase (15-LOX), and shows weak inhibitory activity against acetylcholinesterase (AChE) and glutathione S-transferase (GST). Methyl orsellinate displays contact toxicity against adult Drosophila suzukii. Methyl orsellinate shows anti-HSV-1 activity. Methyl orsellinate can be used in studies related to *Drosophila suzukii* infestation and HSV-1 infection.

Flobufen (VUFB 16066) is a non-steroidal anti-inflammatory agent and cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitor agent. Flobufen inhibits alloantigen-driven cellular immune responses and stimulates phagocytosis of peritoneal cells. Flobufen can improve immunopathological disorders and has an inhibitory effect on rheumatoid arthritis.

5,8,11-Eicosatriynoic acid (ETI) is a lipoxygenase inhibitor that blocks LTC4 biosynthesis in mast cell tumor cells.

5-LOX-IN-2, an inhibitor of 5-lipoxygenase (5-LOX) with an IC₅₀ of 0.33 μM, inhibits 5-LOX in a dose-dependent manner . 5-LOX-IN-2, reduces the cell viability of renal cancer cells and induces apoptosis, can be used for cancer research.