| Identification | Back Directory | [Name]
4-BENZYL-2-METHYL-1,2,4-THIADIAZOLIDINE-3,5-DIONE | [CAS]
327036-89-5 | [Synonyms]
NP 01139
TDZD-8/TDZD8
TDZD-8, >=98%
GSK-3InhibitorI,TDZD-8
1,2,4-Thiadiazolidine-3,5-dione,2-Methyl-4-(phenylMethyl)-
4-Benzyl-2-methyl-[1,2,4]thiadiazolidine-3,5-dione TDZD-8 | [Molecular Formula]
C10H10N2O2S1 | [MDL Number]
MFCD04973552 | [MOL File]
327036-89-5.mol | [Molecular Weight]
222.26 |
| Chemical Properties | Back Directory | [Appearance]
White Solid | [Melting point ]
63-64.4 °C
| [Boiling point ]
335.5±35.0 °C(Predicted) | [density ]
1.375±0.06 g/cm3(Predicted) | [storage temp. ]
2-8°C
| [solubility ]
DMSO: 18 mg/mL
| [form ]
needles
| [pka]
-2.08±0.20(Predicted) | [color ]
white
|
| Hazard Information | Back Directory | [Chemical Properties]
White Solid | [Uses]
Glycogen Synthase Kinase-3? is a highly conserved ubiquitously expressed serine/threonine protein kinase involved in signal transduction cascades of multiple cellular processes. TDZD-8 is a thiadiazolidinone (TDZD) analogue that acts as a highly selectiv | [Definition]
ChEBI: TDZD-8 is a member of the class of thiadiazolidines that is 1,2,4-thiadiazolidine-3,5-dione which is substituted by a methyl group at position 2 and by a benzyl group at position 4. It is a non-ATP competitive inhibitor of glycogen synthase kinase 3beta (GSK3beta). An experimental compound which was being developed for the potential treatment of Alzheimer's disease. It has a role as an EC 2.7.11.26 (tau-protein kinase) inhibitor, an apoptosis inducer, an antineoplastic agent, a neuroprotective agent and an anti-inflammatory agent. It is a thiadiazolidine and a member of benzenes. | [General Description]
A cell-permeable, thiadiazolidinone (TDZD) analog that acts as a highly selective, non-ATP-competitive inhibitor of GSK-3β (IC50 = 2 μM). Inhibits Flt-3 and PKC activities (IC50 = 673 nM and 1.4-5.5 μM, respectively). Does not significantly affect the activities of Cdk1/cyclin B, CK-II, PKA, or PKC (IC50 >100 μM). Shown to inhibit collagen- and thrombin-induced platelet aggregation. | [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 | [storage]
Store at -20°C | [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. |
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