NADPH Oxidase Inhibitor

Diphenyleneiodonium chloride is a NADPH oxidase (NOX) inhibitor and also functions as a TRPA1 activator with an EC₅₀ of 1 to 3 μM. Diphenyleneiodonium chloride selectively inhibits intracellular reactive oxygen species.

GSK2795039 is a NADPH oxidase 2 (NOX2) inhibitor with a mean pIC₅₀ of 6 in different cell-free assays. GSK2795039 inhibits reactive oxygen species (ROS) production and NADPH consumption. GSK2795039 reduces apoptosis.

Setanaxib (GKT137831) is a selective NADPH oxidase (NOX1/4) inhibitor with K_is of 140 and 110 nM, respectively.

GK-136901 is an orally active, dual Nox1/Nox4 NADPH oxidase inhibitor with a K_i of 160 nM for Nox1 and 165 nM for Nox4. GK-136901 potently blocks high glucose-induced intracellular reactive oxygen species production, p38-MAPK phosphorylation, and upregulation of TGF-β1/2 and fibronectin (fibronectin) in renal cells. GK-136901 also inhibits the proliferation of mouse pulmonary vascular cells under hypoxic conditions. GK-136901 is applicable to the research on the pathogenesis of type 2 diabetic nephropathy, high glucose-related renal lesions and pulmonary hypertension.

STAT3/NF-κB-IN-3 is an orally active STAT3/NF-κB inhibitor with anti-inflammatory and antioxidant activities, which specifically blocks the phosphorylation of NF-κB and STAT3 proteins. STAT3/NF-κB-IN-3 downregulates the expression of iNOS and NOX-2 in macrophages, reduces intracellular levels of ROS and MDA, and upregulates the expression of antioxidant genes at the same time. In a mouse model of acute liver failure induced by LPS/D-GalN, STAT3/NF-κB-IN-3 alleviates liver necrosis and inflammatory cell infiltration, and reduces the release of pro-inflammatory cytokines such as IL-6 and IL-12 via the TLR4 pathway. STAT3/NF-κB-IN-3 can be used in studies related to acute liver failure.

Apocynin is a selective NADPH-oxidase inhibitor with an IC₅₀ of 10 μM. Apocynin improves acute lung inflammation in Carrageenan (HY-125474)-induced pleurisy mice model. Apocynin can also be used for cancer research. Apocynin reverses the aging process in mesenchymal stem cells to promote osteogenesis and increases bone mass.

VAS2870 is a NADPH oxidase (NOX) inhibitor.

GLX351322 is an inhibitor of NADPH oxidase 4 (Nox4), and inhibits hydrogen peroxide production from NOX4-overexpressing cells with an IC₅₀ of 5 μM.

ML171 (2-Acetylphenothiazine;2-APT) is a potent and selective NADPH oxidase 1 (Nox1) inhibitor that blocks Nox1-dependent ROS generation, with an IC₅₀ of 0.25 μM in HEK293-Nox1 confirmatory assay.

APX-115 (Ewha-18278) is a potent, orally active pan NADPH oxidase (Nox) inhibitor with K_i values of 1.08 μM, 0.57 μM, and 0.63 μM for Nox1, Nox2 and Nox4, respectively. APX-115 effectively prevents kidney injury.

gp91 ds-tat, a biological active peptide, is a NADPH oxidase 2 (Nox2) inhibitor. gp91 ds-tat blocks NADPH oxidase-dependent superoxide production. gp91 ds-tat ameliorates high glucose-induced increase in total ROS, LPOs and iron levels. gp91 ds-tat inhibits homocysteine (Hcy)-induced activation of NLRP3 inflammasomes and restores Hcy-inhibited lysosomal TRPML1 channel activity. gp91 ds-tat improves cerebrovascular and cognitive function in APP/PS1 mice. gp91 ds-tat can be used for the study of Alzheimer’s disease (AD), glomerular inflammation and cardiovascular disease.

Prochlorperazine dimaleate is an orally active phenothiazine-type dopamine D2 receptor (D2R) antagonist. Prochlorperazine exhibits anti-cancer activity in vitro against various cancer cell lines. Prochlorperazine dimaleate exhibits IC₅₀ values of 6.4 μM, 4.5 μM and 2.3 μM for NOX1, NOX2 and NOX5, respectively. Prochlorperazine dimaleate has antedesmosidic activity against dengue virus (DENV). Prochlorperazine dimaleate can be used for research on nausea, vomiting, migraine, and schizophrenia.

MJ-33 lithium salt is a competitive phospholipase A₂ (PLA₂) inhibitor with an IC₅₀ of 0.3 μM. MJ-33 lithium salt inhibits NOX2 activation and reduces ROS production by blocking the PLA₂ activity of Prdx6. MJ-33 lithium salt effectively inhibits the activity of acidic PLA₂ (pH 4.0) and reduces the degradation of alveolar surfactant phosphatidylcholine (PC), but exerts no effect on alkaline PLA₂ (pH 8.5). MJ-33 lithium salt significantly alleviates lung oxidative injury induced by ischemia-reperfusion (I/R). MJ-33 lithium salt significantly inhibits the invasion, migration and adhesion abilities of prostate cancer cells by suppressing the MAPK, AKT, NF-κB and AP-1 signaling pathways. MJ-33 lithium salt can be used for the research of ROS-related diseases and prostate cancer.

Luteolinidin chloride is a deoxyanthocyanidin isolated from the plant Sorghum bicolor with antioxidant activity. Luteolinidin chloride is a potent CD38 inhibitor (K_i=11.4 μM) and protects the heart from ischemia/reperfusion injury by preserving endothelial nitric oxide synthase (eNOS) function and preventing endothelial dysfunction. Luteolinidin chloride is also a competitive inhibitor of tyrosinase (IC₅₀=3.7 μM) and blocks the production of melanin.

Phox-I2 is a selective inhibitor of p67^phox-Rac1 interaction, binds to p67^phox with high affinity with a K_d of ~150 nM. Phox-I2 is a NADPH oxidase 2 (NOX2) inhibitor and inhibits reactive oxygen species (ROS) production.

GKT136901 is a potent, selective and orally active inhibitor of NADPH oxidase (NOX1/4), with K_is of 160 and 165 nM, respectively. GKT136901 is also a selective and direct scavenger of peroxynitrite. GKT136901 can be used for the research of diabetic nephropathy, stroke, and neurodegeneration. GKT136901 also has anti-inflammatory activity.

NoxA1ds is a potent and highly selective NADPH oxidase 1 (NOX1) inhibitor (IC₅₀=20 nM). NoxA1ds inhibits NOX1-derived O^2- production in HT-29 human colon cancer cells. NoxA1ds attenuates VEGF-induced human pulmonary artery endothelial cell migration under hypoxic conditions in vitro. NoxA1ds can be used in the study of hypertension, atherosclerosis and tumors.

GKT136901 hydrochloride is a potent, selective and orally active inhibitor of NADPH oxidase (NOX1/4), with K_is of 160 and 165 nM, respectively. GKT136901 hydrochloride is also a selective and direct scavenger of peroxynitrite. GKT136901 hydrochloride can be used for the research of diabetic nephropathy, stroke, and neurodegeneration. GKT136901 hydrochloride also has anti-inflammatory activity.

APX-115 free base (Ewha-18278 free base) is a potent, orally active pan NADPH oxidase (Nox) inhibitor with K_i values of 1.08 μM, 0.57 μM, and 0.63 μM for Nox1, Nox2 and Nox4, respectively. APX-115 free base effectively prevents kidney injury.

GLX481304 is a specific inhibitor of Nox-2 and -4, with IC₅₀s of 1.25 μM. GLX481304 suppresses ROS production in isolated mouse cardiomyocytes and improves cardiomyocyte contractility. GLX481304 can be used for research of ischemic injury to the heart.