327036-89-5

Basic information

• Product Name: 4-BENZYL-2-METHYL-1,2,4-THIADIAZOLIDINE-3,5-DIONE
• Synonyms: GSK-3InhibitorI,TDZD-8;NP 01139;1,2,4-Thiadiazolidine-3,5-dione,2-Methyl-4-(phenylMethyl)-;TDZD-8/TDZD8;4-Benzyl-2-methyl-[1,2,4]thiadiazolidine-3,5-dione TDZD-8;TDZD-8, >=98%
• CAS NO: 327036-89-5
• Molecular Formula: C10H10N2O2S1
• Molecular Weight: 222.26
• Product Categories: Inhibitors;Amines;Aromatics;Sulfur & Selenium Compounds;Other Enzyme Inhibitors and Activators.;Akt;mTOR;PI3K
• Mol File: 327036-89-5.mol
• Article Data: 2

Chemical Properties

• Melting Point: 63-64.4 °C
• Boiling Point: 335.5 °C at 760 mmHg
• Flash Point: 156.7 °C
• Appearance: white/needles
• Density: 1.375 g/cm³
• Vapor Pressure: 0.000119mmHg at 25°C
• Refractive Index: 1.645
• Storage Temp.: 2-8°C
• Solubility: DMSO: 18 mg/mL
• PKA: -2.08±0.20(Predicted)
• CAS DataBase Reference: 4-BENZYL-2-METHYL-1,2,4-THIADIAZOLIDINE-3,5-DIONE(CAS DataBase Reference)
• NIST Chemistry Reference: 4-BENZYL-2-METHYL-1,2,4-THIADIAZOLIDINE-3,5-DIONE(327036-89-5)
• EPA Substance Registry System: 4-BENZYL-2-METHYL-1,2,4-THIADIAZOLIDINE-3,5-DIONE(327036-89-5)

Safety Data

• Hazard Codes: Xi
• Statements: 43
• Safety Statements: 36/37
• WGK Germany: 3
• Hazardous Substances Data: 327036-89-5(Hazardous Substances Data)

Usage

Description

4-BENZYL-2-METHYL-1,2,4-THIADIAZOLIDINE-3,5-DIONE, also known as TDZD-8, is a thiadiazolidinone (TDZD) analogue that exhibits high selectivity for Glycogen Synthase Kinase-3 (GSK-3), a serine/threonine protein kinase involved in various cellular processes. TDZD-8 is a promising compound for studying the role of GSK-3 in different biological systems.
Used in Pharmaceutical Research:
TDZD-8 is used as a selective inhibitor for studying the role of GSK-3 in various cellular processes and diseases. Its high selectivity makes it a valuable tool for understanding the function of GSK-3 and its potential as a therapeutic target.
Used in Cancer Research:
In the field of cancer research, TDZD-8 is used to study the role of GSK-3 in maintaining the MLL leukemia stem cell transcriptional program. This helps researchers understand the mechanisms underlying the development and progression of leukemia and identify potential therapeutic targets.
Used in Neuroscience Research:
TDZD-8 is also used in neuroscience research to analyze its effect on the neural functions of the mouse olfactory bulb. This application helps researchers explore the role of GSK-3 in neural development and function, as well as its potential implications for neurological disorders.

Biological Activity

tdzd-8 is an inhibitor of glycogen synthase kinase-3β (gsk-3β) with ic50 value of 1.4μm [1].tdzd-8 is a potent inhibitor of gsk-3β. it is found to act as a noncompetitive inhibitor of atp binding. tdzd-8 is selective against gsk-3β over other protein kinases including pka, casein kinase ii and cyclin dependent kinase 1 (cdk-1/cyclin b). however, it is also reported that tdzd-8 can inhibit the protein kinase c isoforms pkcβi and pkcδ with ic50 values of 1.4μm and 1.1μm, respectively [1, 2].in cellular assay, tdzd-8 is found to decrease pdt-induced necrosis of neurons and decrease pdt-induced apoptosis of glial cells through inhibiting gsk-3β as well as pkc. besides that, tdzd-8 also has anti-leukemia activity in many primary human leukemia cells. it is probably due to its inhibition of pkc and flt3 [3].

Biochem/physiol Actions

Primary TargetGsk-3β

references

[1] komandirov m a, knyazeva e a, fedorenko y p, et al. on the role of phosphatidylinositol 3-kinase, protein kinase b/akt, and glycogen synthase kinase-3β in photodynamic injury of crayfish neurons and glial cells. journal of molecular neuroscience, 2011, 45(2): 229-235.[2] martinez a, alonso m, castro a, et al. first non-atp competitive glycogen synthase kinase 3 β (gsk-3β) inhibitors: thiadiazolidinones (tdzd) as potential drugs for the treatment of alzheimer's disease. journal of medicinal chemistry, 2002, 45(6): 1292-1299.[3] guzman m l, li x, corbett c a, et al. rapid and selective death of leukemia stem and progenitor cells induced by the compound 4-benzyl, 2-methyl, 1, 2, 4-thiadiazolidine, 3, 5 dione (tdzd-8). blood, 2007, 110(13): 4436-4444.

InChI:InChI=1/C10H10N2O2S/c1-11-9(13)12(10(14)15-11)7-8-5-3-2-4-6-8/h2-6H,7H2,1H3

Upstream product

• 55000-02-7 N-benzyl-S-chloroisothiocarbamoyl chloride 
• 622-78-6 Benzyl isothiocyanate 
• 624-83-9 methyl isocyanate 

Relevant articles and documents

N-benzylpiperidine derivatives of 1,2,4-thiadiazolidinone as new acetylcholinesterase inhibitors

A new family of 1,2,4-thiadiazolidinone derivatives containing the N-benzylpiperidine fragment has been synthesised. The acetylcholinesterase (AChE) inhibitory activity of all compounds was measured using Ellman's method and some of them turned out to be as potent as tacrine. Furthermore, compound 13 was as active as tacrine in reversing the blockade induced by tubocurarine at rat neuromuscular junction. Additionally, receptor binding studies provided new lead compounds for further development of α2-adrenergic and sigma-receptor antagonists. Molecular dynamic simulation using X-ray crystal, structure of AChE from Torpedo californica was used to explain the possible binding mode of these new compounds. (C) 2000 Editions scientifiques et medicales Elsevier SAS.