264218-23-7 Usage
Description
SB-415286 is a potent and selective cell-permeable, ATP-competitive inhibitor of glycogen synthase kinase 3 (GSK3) with an IC50 value of 78 nM (similar potency for GSK3β) and a Ki value of 31 nM. It is a member of the class of maleimides carrying 3-chloro-4-hydroxyphenylamino and 2-nitrophenyl substituents at positions 3 and 4, respectively. SB 415286 has been used to study the effects of GSK3 inhibition on various cell functions, including cell division, apoptosis, and inflammation.
Uses
Used in Pharmaceutical Research:
SB-415286 is used as a research tool for studying the role of GSK3 in various cellular processes. Its inhibition of GSK3 activity allows researchers to investigate the effects of GSK3 modulation on cell functions such as cell division, apoptosis, and inflammation.
Used in Neuroblastoma Cell Studies:
SB-415286 is used as a therapeutic agent to treat neuroblastoma cells, a type of cancer commonly associated with the deregulation of GSK3 activity. By inhibiting GSK3, SB-415286 can help study the effect of GSK3 inhibition on cell proliferation and potentially lead to the development of new treatments for neuroblastoma.
Used in Neuroprotection:
SB-415286 is used as a neuroprotective agent, as it has been shown to protect primary neurons from death induced by the PI3-kinase pathway. This property makes it a valuable compound for studying the mechanisms of neuroprotection and developing potential therapies for neurodegenerative diseases.
Used in Glycogen Synthesis Stimulation:
SB-415286 is used as a stimulator of glycogen synthesis in the Chang human liver cell line, with an EC50 value of 2.9 μM. This application allows researchers to study the regulation of glycogen synthesis and its potential role in metabolic diseases and other conditions.
Biological Activity
Potent and selective glycogen synthase kinase-3 (GSK-3) inhibitor (K i = 31 nM for GSK-3 α ); competes with ATP. Has minimal activity against 24 other protein kinases (IC 50 > 10 μ M). Stimulates glycogen synthesis, gene transcription and is neuroprotective.
Biochem/physiol Actions
SB 415286 is a small molecule inhibitor of GSK-3 in muscle and fat cells. SB 415286 induces activation of glycogen synthase and regulates the transport glucose. SB 415286 reduces the systemic inflammation induced by endotoxic shock in rat model of acute colitis. It increases the axonal growth and promotes the recovery of injured adult CNS neurons. SB 415289 is implicated in inducing chromosome instability when used as therapeutic agents.
references
selective small molecule inhibitors of glycogen synthase kinase-3 modulate glycogen metabolism and gene transcription. chem biol. 2000 oct;7(10):793-803.selective small-molecule inhibitors of glycogen synthase kinase-3 activity protect primary neurones from death. j neurochem. 2001 apr;77(1):94-102.role of glycogen synthase kinase 3beta in rapamycin-mediated cell cycle regulation and chemosensitivity. cancer res. 2005 mar 1;65(5):1961-72.pharmacologic modulation of glycogen synthase kinase-3beta promotes p53-dependent apoptosis through a direct bax-mediated mitochondrial pathway in colorectal cancer cells. cancer res. 2005 oct 1;65(19):9012-20.glycogen synthase kinase 3 inhibition slows mitochondrial adenine nucleotide transport and regulates voltage-dependent anion channel phosphorylation. circ res. 2008 oct 24;103(9):983-91. doi: 10.1161/circresaha.108.178970. epub 2008 sep 18.glycogen synthase kinase 3β inhibitors protect hippocampal neurons from radiation-induced apoptosis by regulating mdm2-p53 pathway. cell death differ. 2012 mar;19(3):387-96. doi: 10.1038/cdd.2011.94. epub 2011 jul 8.a gsk-3β inhibitor protects against radiation necrosis in mouse brain. int j radiat oncol biol phys. 2014 jul 15;89(4):714-21. doi: 10.1016/j.ijrobp.2014.04.018.
Check Digit Verification of cas no
The CAS Registry Mumber 264218-23-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,6,4,2,1 and 8 respectively; the second part has 2 digits, 2 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 264218-23:
(8*2)+(7*6)+(6*4)+(5*2)+(4*1)+(3*8)+(2*2)+(1*3)=127
127 % 10 = 7
So 264218-23-7 is a valid CAS Registry Number.
InChI:InChI=1/C16H10ClN3O5/c17-10-7-8(5-6-12(10)21)18-14-13(15(22)19-16(14)23)9-3-1-2-4-11(9)20(24)25/h1-7,21H,(H2,18,19,22,23)
264218-23-7Relevant articles and documents
3-Anilino-4-arylmaleimides: Potent and selective inhibitors of glycogen synthase kinase-3 (GSK-3)
Smith, David G.,Buffet, Marianne,Fenwick, Ashley E.,Haigh, David,Ife, Robert J.,Saunders, Martin,Slingsby, Brian P.,Stacey, Rachel,Ward, Robert W.
, p. 635 - 639 (2001)
Potent 3-anilino-4-arylmaleimide glycogen synthase kinase-3 (GSK-3) inhibitors have been prepared using automated array methodology. A number of these are highly selective, having little inhibitory potency against more than 20 other protein kinases.
