478482-75-6

Basic information

• Product Name: 2-THIO(3-IODOBENZYL)-5-(1-PYRIDYL)-[1,3,4]-OXADIAZOLE
• Synonyms: TIBPO;2-THIO(3-IODOBENZYL)-5-(1-PYRIDYL)-[1,3,4]-OXADIAZOLE;GLYCOGEN SYNTHASE KINASE-3 INHIBITOR II;GSK-3 INHIBITOR II;Pyridine, 4-[5-[[(3-iodophenyl)Methyl]thio]-1,3,4-oxadiazol-2-yl]-;4-[5-[[(3-Iodophenyl)methyl]thio]-1,3,4-oxadiazol-2-yl]pyridine;2-[(3-iodophenyl)methylsulfanyl]-5-pyridin-4-yl-1,3,4-oxadiazole;GSK3.beta. Inhibitor II
• CAS NO: 478482-75-6
• Molecular Formula: C₁₄H₁₀IN₃OS
• Molecular Weight: 395.22
• Mol File: 478482-75-6.mol
• Article Data: 5

Chemical Properties

• Boiling Point: 532.6±60.0 °C(Predicted)
• Appearance: /
• Density: 1.79±0.1 g/cm3(Predicted)
• Storage Temp.: -20C
• Solubility: ≤3mg/ml in DMSO;10mg/ml in dimethyl formamide
• PKA: 0.97±0.10(Predicted)
• CAS DataBase Reference: 2-THIO(3-IODOBENZYL)-5-(1-PYRIDYL)-[1,3,4]-OXADIAZOLE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-THIO(3-IODOBENZYL)-5-(1-PYRIDYL)-[1,3,4]-OXADIAZOLE(478482-75-6)
• EPA Substance Registry System: 2-THIO(3-IODOBENZYL)-5-(1-PYRIDYL)-[1,3,4]-OXADIAZOLE(478482-75-6)

Safety Data

• Hazardous Substances Data: 478482-75-6(Hazardous Substances Data)

Usage

Biological Activity

gsk-3β inhibitor ii is a gsk-3β inhibitor.glycogen synthase kinase-3 (gsk-3), a protein-serine kinase, is implicated in the hormonal control of various regulatory proteins. a number of substrates have been identified, which implicates gsk-3 in the regulation of several physiological processes. moreover, it has been reported that compounds that specifically inhibit gsk-3 activity may be useful in the treatment of diabetes.

in vitro

in a previous study, by using a virtual screening strategy based on a methodology derived from the cats molecular descriptor, a novel compound class including gsk-3β inhibitor ii with inhibitory activity against the gsk-3 enzyme was identified via scaffold hopping. gsk-3β inhibitor ii was found to be a potent inhibitor of gsk-3β with the ic50 value of 390 nm. however, gsk-3β inhibitor ii was not able to inhibit another gsk-3 isoform, gsk-3α [1]. another study found that gsk-3β inhibitor ii could block the functional regulation of p53 through inhibiting gsk-3β, decreasing mdm2 levels, and modulating mitochondrial p53 apoptotic signaling [2].

IC 50

390 nm for gsk-3β

references

[1] naerum, l. ,nrskov-lauritsen, l. and olesen, p.h. scaffold hopping and optimization towards libraries of glycogen synthase kinase-3 inhibitors. bioorg.med.chem.lett. 12(11), 1525-1528 (2002).[2] watcharasit, p. ,bijur, g.n.,song, l., et al. glycogen synthase kinase-3beta (gsk3beta) binds to and promotes the actions of p53. j.biol.chem. 278(49), 49972-48879 (2003).

Upstream product

• 15264-63-8 5-(4-pyridinyl)-1,3,4-oxadiazole-2-thiol 
• 54-85-3 isoniazid 
• 49617-83-6 m-Iodobenzyl bromide 
• 1570-45-2 isonicotinic acid ethylester 

Relevant articles and documents

SMALL MOLECULE INHIBITORS OF SUPEROXIDE DISMUTASE EXPRESSION

Disclosed are new small molecules and the uses thereof for inhibiting superoxide dismutase (SOD) expression. Also disclosed are pharmaceutical compositions comprising the small molecule inhibitors which may be administered in methods of treating diseases or disorders associated with elevated SOD expression or activity, including neurological diseases and disorders such as amyotrophic lateral sclerosis (ALS).

Discovery of 1,3,4-oxidiazole scaffold compounds as inhibitors of superoxide dismutase expression

The treatment of neurodegenerative diseases is difficult because of multiple etiologies and the interplay of genetics and environment as precipitating factors. In the case of amyotrophic lateral sclerosis (ALS), we have knowledge of a handful of genes that cause disease when mutated. However, drugs to counteract the effect of genetic mutations have not yet been found. One of the causative genes, Cu, Zn-superoxide dismutase (SOD1) is responsible for about 10-15% of the genetically linked autosomal dominant disease. Our rationale was that compounds that reduce expression of the mutant protein would be beneficial to slow onset and/or disease progression. We screened candidate compounds using a cell-based in vitro assay for those that reduce mutant SOD1 (G93A) protein expression. This led to the discovery of 2-[3-iodophenyl) methylsulfanyl]-5pyridin-4-yl-1,3,4-oxadiazole, a known protein kinase inhibitor that decreases G93A-SOD1 expression in vitro and in the brain and spinal cord in vivo. However, this compound has a biphasic dose response curve and a likely toxophore which limit its therapeutic window for chronic disease such as ALS. Therefore, we designed and tested a focused library of analogs for their ability to decrease SOD1 expression in vitro. This exercise resulted in the identification of a lead compound with improved drug-like characteristics and activity. Development of small molecules that reduce the expression of etiologically relevant toxic proteins is a strategy that may also be extended to familial ALS linked to gain of function mutations in other genes.

Scaffold hopping and optimization towards libraries of glycogen synthase kinase-3 inhibitors

Using a virtual screening strategy based on a methodology derived from the CATS molecular descriptor, a novel compound class with inhibitory activity against the GSK-3 enzyme was identified through scaffold hopping. These compounds were readily synthesize