GTS-21 dihydrochloride

"目录号: HY-14564A

Membrane Transporter/Ion ChannelNeuronal Signaling-

GTS-21二盐酸盐是一种选择性α7烟碱型乙酰胆碱受体 (α7nAChR) 激动剂。

nAChR

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生物活性

Description

GTS-21 dihydrochloride is a selective α7 nicotinic acetylcholine receptor agonist, has recently been established as a promising treatment for inflammation. Target: nAChRin vitro: GTS-21 is one of the most potent α7nAChR agonists, has been reported to attenuate pro-inflammatory cytokine production, improve outcomes in sepsis models, pancreatitis, and ischemia-reperfusion injury, and inhibit the production of endotoxin-induced TNF in lung tissue. In addition, recent studies have demonstrated that GTS-21 inhibits the activities of endothelial cells and monocyte macrophages, as well as the secretion of pro-inflammatory cytokines in peripheral blood samples, by regulating the JAK2-STAT3 pathway. [1] in vivo: In septic animals, GTS-21 significantly ameliorated GI motility, lowered systemic and colonic levels of IL-6, decreased colonic permeability, and decreased the number of positive cultures obtained from blood and mesenteric lymph nodes. Splenectomy prevented animals from developing sepsis-induced ileus. Chrna7 mice displayed a more severe septic phenotype, whereas GTS-21 remarkably was also beneficial in these animals. [2]

Clinical Trial

NCT02538081

VA Office of Research and Development-University of Colorado, Denver

Schizophrenia

August 2015

Phase 1-Phase 2

NCT01400477

University of Colorado, Denver-National Institute of Mental Health (NIMH)

Schizophrenia-Schizoaffective Disorder

July 2011

Phase 2

NCT02458313

University of Colorado, Denver

Obesity

November 2015

Phase 1

NCT00414622

CoMentis

Alzheimer Disease

November 2006

Phase 2

NCT02111551

University of Colorado, Denver

Autism

June 2015

Phase 1

NCT00255918

University of Colorado, Denver-National Institute of Mental Health (NIMH)

Schizophrenia-Psychotic Disorders

March 2004

Phase 1

NCT00783068

Radboud University-CoMentis

Endotoxemia-Sepsis-Vagal Activity

August 2008

NCT02432066

University of Florida

Tobacco Use Disorder

June 29, 2017

Phase 2

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References

[1].Yue Y, et al. GTS-21 attenuates lipopolysaccharide-induced inflammatory cytokine production in vitro by modulating the Akt and NF-κB signaling pathway through the α7 nicotinic acetylcholine receptor. Int Immunopharmacol. 2015 Dec;29(2):504-12.

[2].Nullens S, et al. EFFECT OF GTS-21, AN ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR AGONIST, ON CLP-INDUCED INFLAMMATORY, GASTROINTESTINAL MOTILITY, AND COLONIC PERMEABILITY CHANGES IN MICE. Shock. 2016 Apr;45(4):450-9.

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