NADPH oxidase inhibitors: a patent review

Kim, Jung Ae; Neupane, Ganesh Prasad; Lee, Eung Seok; Jeong, Byeong Seon; Park, Byung Chul; Thapa, Pritam

doi:10.1517/13543776.2011.584870

Cited by 64 publications

(54 citation statements)

References 68 publications

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“…Of the many enzymes that are potential therapeutic targets are Noxs. Due to this, there has been enormous interest in the development of agents that inhibit Noxs in an isoform-specific manner (91,102,194,197). Different strategies have been employed, including smallmolecule inhibitors, peptide Nox inhibitors, and siRNAS.…”

Section: Noxs As Putative Targets In the Treatment Of Hypertensionmentioning

confidence: 99%

“…Different strategies have been employed, including smallmolecule inhibitors, peptide Nox inhibitors, and siRNAS. Several pharmacological compounds have been registered as Nox inhibitors in the patent literature (102). First-generation Nox inhibitors, including apocynin and diphenylene iodinium, are non specific, lack selectivity, and have multiple ''offtarget'' side effects.…”

Section: Noxs As Putative Targets In the Treatment Of Hypertensionmentioning

confidence: 99%

“…Newer-generation NOX inhibitors are more specific and selective. To date, two different classes of compounds have been claimed as potent selective and orally active bioavailable Nox inhibitors: pyrazolopyridines (GKT136901 and GKT137831) and triazolopyrimidine derivatives (VAS2870 and VAS3947) (39,91,102,194,197). These agents target mainly Nox1 and Nox4, and, apparently, have a few ''off-target'' side effects (22, 217).…”

Section: Noxs As Putative Targets In the Treatment Of Hypertensionmentioning

confidence: 99%

See 2 more Smart Citations

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Montezano

Touyz²

2014

Antioxidants & Redox Signaling

229

177

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Significance: Reactive oxygen species (ROS) are signaling molecules that are important in physiological processes, including host defense, aging, and cellular homeostasis. Increased ROS bioavailability and altered redox signaling (oxidative stress) have been implicated in the onset and/or progression of chronic diseases, including hypertension. Recent Advances: Although oxidative stress may not be the only cause of hypertension, it amplifies blood pressure elevation in the presence of other pro-hypertensive factors, such as salt loading, activation of the renin-angiotensin-aldosterone system, and sympathetic hyperactivity, at least in experimental models. A major source for ROS in the cardiovascular-renal system is a family of nicotinamide adenine dinucleotide phosphate oxidases (Noxs), including the prototypic Nox2-based Nox, and Nox family members: Nox1, Nox4, and Nox5. Critical Issues: Although extensive experimental data support a role for increased ROS levels and altered redox signaling in the pathogenesis of hypertension, the role in clinical hypertension is unclear, as a direct causative role of ROS in blood pressure elevation has yet to be demonstrated in humans. Nevertheless, what is becoming increasingly evident is that abnormal ROS regulation and aberrant signaling through redoxsensitive pathways are important in the pathophysiological processes which is associated with vascular injury and target-organ damage in hypertension. Future Directions: There is a paucity of clinical information related to the mechanisms of oxidative stress and blood pressure elevation, and a few assays accurately measure ROS directly in patients. Such further ROS research is needed in humans and in the development of adequately validated analytical methods to accurately assess oxidative stress in the clinic. Antioxid. Redox Signal. 20,[164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182]

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Section: Noxs As Putative Targets In the Treatment Of Hypertensionmentioning

confidence: 99%

Section: Noxs As Putative Targets In the Treatment Of Hypertensionmentioning

confidence: 99%

Section: Noxs As Putative Targets In the Treatment Of Hypertensionmentioning

confidence: 99%

See 1 more Smart Citation

Reactive Oxygen Species, Vascular Noxs, and Hypertension: Focus on Translational and Clinical Research

Montezano

Touyz²

2014

Antioxidants & Redox Signaling

229

177

View full text Add to dashboard Cite

show abstract

“…To date six human isoforms have been isolated (Nox 1, 3, 4, 5, and Duox 1 and 2) (19,20). They utilize a system that is dependent on NADPH, although, NADH can also be used as substrate (21). As a result they are referred to as NAD(P)H oxidases (12,22).…”

Section: Ros Generation In Non Phagocytic Conditionsmentioning

confidence: 99%

Oxidative Stress in Human Health and Disease

Quaye¹

2012

Insight and Control of Infectious Disease in Global Scenario

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“…Several small molecule and peptide inhibitors of the NOX enzymes have been developed and are showing promise in experimental studies, but issues of specificity, potency and toxicity militate against any of the existing compounds as candidates for drug development (Kim et al 2011;Williams & Griendling 2007). In a recent study, apocynin, a proven NADPH oxidase inhibitor, attenuated albuminuria, improved kidney structure (glomerular and mesangial expansion) and reduced oxidative stress (urinary 8-OHdG and malondialdehyde) in aged Otsuka Long Evans Tokushima Fatty (OLETF) rats (Nam et al 2009).…”

Section: Nox Inhibitorsmentioning

confidence: 99%