Oltipraz

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Oltipraz
Oltipraz.png
Clinical data
ATC code
  • none
Identifiers
  • 4-methyl-5-(2-pyrazinyl)-3-dithiolethione
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.058.833 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C8H6N2S3
Molar mass 226.33 g·mol−1
3D model (JSmol)
  • CC1=C(SSC1=S)C2=NC=CN=C2
  • InChI=1S/C8H6N2S3/c1-5-7(12-13-8(5)11)6-4-9-2-3-10-6/h2-4H,1H3 X mark.svgN
  • Key:CKNAQFVBEHDJQV-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Oltipraz is an organosulfur compound belonging to the dithiolethione class. [1] [2] It acts as a schistosomicide and has been shown in rodent models to inhibit the formation of cancers in the bladder, blood, colon, kidney, liver, lung, pancreas, stomach, and trachea, skin, and mammary tissue. [3] [4] Clinical trials of oltipraz have failed to demonstrate efficacy and have shown significant side effects, including neurotoxicity and gastrointestinal toxicity. [3] Oltipraz has also been shown to generate superoxide radicals, which can be toxic. [5]

Related Research Articles

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<span class="mw-page-title-main">Superoxide dismutase</span> Class of enzymes

Superoxide dismutase (SOD, EC 1.15.1.1) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide (O
2
) radical into ordinary molecular oxygen (O2) and hydrogen peroxide (H
2
O
2
). Superoxide is produced as a by-product of oxygen metabolism and, if not regulated, causes many types of cell damage. Hydrogen peroxide is also damaging and is degraded by other enzymes such as catalase. Thus, SOD is an important antioxidant defense in nearly all living cells exposed to oxygen. One exception is Lactobacillus plantarum and related lactobacilli, which use a different mechanism to prevent damage from reactive O
2
.

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<span class="mw-page-title-main">Reactive oxygen species</span> Highly reactive molecules formed from diatomic oxygen (O₂)

In chemistry and biology, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (O2), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (O2H), superoxide (O2-), hydroxyl radical (OH.), and singlet oxygen. ROS are pervasive because they are readily produced from O2, which is abundant. ROS are important in many ways, both beneficial and otherwise. ROS function as signals, that turn on and off biological functions. They are intermediates in the redox behavior of O2, which is central to fuel cells. ROS are central to the photodegradation of organic pollutants in the atmosphere. Most often however, ROS are discussed in a biological context, ranging from their effects on aging and their role in causing dangerous genetic mutations.

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<span class="mw-page-title-main">Genistein</span> Chemical compound

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<span class="mw-page-title-main">SOD1</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">SOD2</span> Enzyme

Superoxide dismutase 2, mitochondrial (SOD2), also known as manganese-dependent superoxide dismutase (MnSOD), is an enzyme which in humans is encoded by the SOD2 gene on chromosome 6. A related pseudogene has been identified on chromosome 1. Alternative splicing of this gene results in multiple transcript variants. This gene is a member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the superoxide byproducts of oxidative phosphorylation and converts them to hydrogen peroxide and diatomic oxygen. Mutations in this gene have been associated with idiopathic cardiomyopathy (IDC), premature aging, sporadic motor neuron disease, and cancer.

<span class="mw-page-title-main">NFE2L2</span> Human protein and coding gene

Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation, according to preliminary research. In vitro, NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.

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<span class="mw-page-title-main">KEAP1</span> Protein-coding gene in the species Homo sapiens

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References

  1. Prince M, Li Y, Childers A, Itoh K, Yamamoto M, Kleiner HE (March 2009). "Comparison of citrus coumarins on carcinogen-detoxifying enzymes in Nrf2 knockout mice". Toxicology Letters. 185 (3): 180–186. doi:10.1016/j.toxlet.2008.12.014. PMC   2676710 . PMID   19150646.
  2. Ansari MI, Khan MM, Saquib M, Khatoon S, Hussain MK (May 2018). "Dithiolethiones: a privileged pharmacophore for anticancer therapy and chemoprevention". Future Medicinal Chemistry. 10 (10): 1241–1260. doi:10.4155/fmc-2017-0281. PMID   29749746.
  3. 1 2 Zhang Y, Gordon GB (July 2004). "A strategy for cancer prevention: stimulation of the Nrf2-ARE signaling pathway". Molecular Cancer Therapeutics. 3 (7): 885–893. doi: 10.1158/1535-7163.885.3.7 . PMID   15252150.
  4. Iida K, Itoh K, Kumagai Y, Oyasu R, Hattori K, Kawai K, et al. (September 2004). "Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis". Cancer Research. 64 (18): 6424–6431. doi: 10.1158/0008-5472.CAN-04-1906 . PMID   15374950.
  5. Velayutham M, Villamena FA, Fishbein JC, Zweier JL (March 2005). "Cancer chemopreventive oltipraz generates superoxide anion radical". Archives of Biochemistry and Biophysics. 435 (1): 83–88. doi:10.1016/j.abb.2004.11.028. PMID   15680910.