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Small Molecules for Oxidative Stress Applications

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An excess of free radicals causes oxidative stress, an unstable cellular environment that can result from exposure to alcohol, medications, poor nutrition, trauma, cold, toxins, and over-exercise. Free radicals and other reactive oxygen species (ROS) form when cells encounter oxidizing agents or ionizing radiation. ROS can damage DNA, an early step in carcinogenesis; damage to other bio-molecules leads to atherosclerosis, cerebral and heart ischemia-reperfusion injury, rheumatoid arthritis, inflammation, diabetes, aging, neurodegenerative diseases, and other disorders.

Calbiochem® provides high quality small molecules inhibitors for modulating oxidative stress, which have been cited in numerous peer-reviewed publications.


Arginase Inhibitors

Arginase, an Mn2+ metalloenzyme, catalyzes the hydrolysis of L-arginine to yield L-ornithine and urea in ureotelic animals. Based on their distribution, two isoforms of arginase have been described. Due to the reciprocal regulation between arginase and nitric oxide synthase, arginase inhibitors are considered to have therapeutic potential in treating NO-dependent smooth muscle disorders, such as erectile dysfunctions and polyamine induced bronchial constriction ...

Glutathione S-Transferase (GST) Inhibitors

Glutathione S-transferases (GSTs) constitute a family of phase II detoxification isozymes that catalyze the conjugation of glutathione with a number of hydrophobic compounds. Increased expression of GST isozymes has been linked to the development of resistance to alkylating cytostatic drugs. Their deficiency reportedly increases predisposition to various forms of cancer. Hence, GST status may be a useful prognostic factor to determine the clinical outcome of chemotherapy ...

Guanylate Cyclase Inhibitors

Guanylyl cyclase (GC) catalyzes the formation of the second messenger cyclic GMP (cGMP) from GTP and exists in both the soluble and particulate fractions. The soluble enzyme can be regulated by free radicals and nitrovasodialators, whereas the particulate enzyme can be regulated by various peptides. cGMP signaling is mediated by cGMP-activated protein kinases, the cGMP-regulated phosphodiesterases and the cGMP-gated ion channels. The action of cGMP is terminated by the action of cGMP-degrading phosphodiesterases. GC is present either as soluble (sGC) or as membrane-bound enzyme linked to a receptor ...

Nitric Oxide Synthase (NOS) Inhibitors

Nitric oxide (•NO), a highly reactive, diffusible, and unstable radical, plays an important role in the regulation of a wide range of physiological processes, including cellular immunity, angiogenesis, neurotransmission, and platelet aggregation. •NO is synthesized from L-arginine by the action of nitric oxide synthase (NOS) in a two-step oxidation process. NOS is known to exist in three isoforms. Because of the involvement of all the three NOS isozymes in various aspects of signal transduction, NOS inhibitors have gained prominence in the management of ischemic reperfusion injury, hypotensive effects of drugs, and inflammatory response to cytokines ...

Nrf2 Activators: Antioxidants and Neuroprotectors

Nuclear erythroid 2-related factor 2 (Nrf2), a leucine-zipper transcription factor, binds to the antioxidant response element (ARE) and regulates the expression of a large number of genes involved in defense mechanisms. It is also involved in maintaining antioxidant status and in anti-inflammatory responses. Under basal conditions, Nrf2 is bound to the endogenous inhibitor Kelch-like ECH associated protein1 (Keap1), and, upon activation, it translocates to the nucleus. The Nrf2-ARE pathway can be activated under conditions of oxidative stress, infection, and inflammation. Activation of this pathway induces the production of superoxide dismutases, catalase, and glutathione peroxidases, which play a critical role in free radical scavenging. Hence, any disruption in this pathway can lead to excessive oxidative stress and imbalanced inflammatory response. Nrf2 has emerged as a key neuroprotective molecule in neurodegenerative diseases. Alterations in Nrf2 and Keap1 expression and dysregulation of the Nrf2/ARE signaling have been linked to the chronic motor neuron degeneration in amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Hence, this pathway has become an important target for drug discovery in ALS, Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease.