<p style=/line-height:25px/>TDZD-8(NP 01139) is a selective inhibitor of GSK-3, a thiadiazolidinone derivative, non-ATP competitive inhibitor of GSK-3β (IC50 = 2 μM); does not inhibit Cdk-1/cyclin B, CK-II, PKA or PKC at >100 μM.<br>IC50 Value: 2 uM (GSK3β)<br>Target: GSK-3β<br>in vitro: Prophylactic or therapeutic administration of TDZD-8 caused the phosphorylation (Ser(9)) and hence inactivation of GSK-3beta. Infarct volume and levels of S100B protein, a marker of cerebral injury, were reduced by TDZD-8. This was associated with a significant reduction in markers of oxidative stress, apoptosis, and the inflammatory response resulting from cerebral I/R [1]. Notably, cell death was frequently evident within 2 hours or less of TDZD-8 exposure. Cellular and molecular studies indicate that the mechanism by which TDZD-8 induces cell death involves rapid loss of membrane integrity, depletion of free thiols, and inhibition of both the PKC and FLT3 signaling pathways [4].<br>in vivo: Using mouse xenograft models, we demonstrated that LiCl and TDZD-8 significantly suppressed tumor development and growth of subcutaneous xenografts derived from human prostate cancer cells. Similarly, in the TRAMP mice, TDZD-8 and L803-mts reduced the incidence and tumor burden in the prostate lobes [2]. TDZD-8 significantly reduced the degree of pancreas injury, amylase, and lipase serum levels (p < .01); nuclear factor-kappaB activation (p < .01); the production of tumor necrosis factor-alpha and interleukin-1beta (p < .01); the expression of adhesion molecules and neutrophil accumulation (p < .01); the formation of oxygen and nitrogen-derived radicals (p < .01); the degree of lipid peroxidation (p < .01); the expression of transforming growth factor-beta and vascular endothelial growth factor (p < .01); and-ultimately-the mortality rate (p < .01) in rats [3].<br><br></p>
| Catalog Number | I003158 |
| CAS Number | 327036-89-5 |
| Synonyms | 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione |
| Molecular Formula | C₁₀H₁₀N₂O₂S |
| Purity | ≥95% |
| Target | GSK-3 |
| Solubility | 10 mM in DMSO |
| Storage | 3 years -20C powder |
| IC50 | 2 uM (GSK3β) |
| InChI | InChI=1S/C10H10N2O2S/c1-11-9(13)12(10(14)15-11)7-8-5-3-2-4-6-8/h2-6H,7H2,1H3 |
| InChIKey | JDSJDASOXWCHPN-UHFFFAOYSA-N |
| SMILES | CN1C(=O)N(C(=O)S1)CC2=CC=CC=C2 |
| Reference | </br>1:GSK-3β inhibitor TDZD-8 reduces neonatal hypoxic-ischemic brain injury in mice. Huang S, Wang H, Turlova E, Abussaud A, Ji X, Britto LR, Miller SP, Martinez A, Sun HS, Feng ZP.CNS Neurosci Ther. 2017 May;23(5):405-415. doi: 10.1111/cns.12683. Epub 2017 Mar 2. PMID: 28256059 </br>2:Activation of AKT/GSK3β pathway by TDZD-8 attenuates kainic acid induced neurodegeneration but not seizures in mice. Bhowmik M, Khanam R, Saini N, Vohora D.Neurotoxicology. 2015 Jan;46:44-52. doi: 10.1016/j.neuro.2014.11.008. Epub 2014 Nov 29. PMID: 25453207 </br>3:Imaging pulmonary NF-kappaB activation and therapeutic effects of MLN120B and TDZD-8. Ansaldi D, Hod EA, Stellari F, Kim JB, Lim E, Roskey M, Francis KP, Singh R, Zhang N.PLoS One. 2011;6(9):e25093. doi: 10.1371/journal.pone.0025093. Epub 2011 Sep 22. PMID: 21966423 Free PMC Article</br>4:Inhibition of glioblastoma growth by the thiadiazolidinone compound TDZD-8. Aguilar-Morante D, Morales-Garcia JA, Sanz-SanCristobal M, Garcia-Cabezas MA, Santos A, Perez-Castillo A.PLoS One. 2010 Nov 8;5(11):e13879. doi: 10.1371/journal.pone.0013879. PMID: 21079728 Free PMC Article</br>5:Treatment with the glycogen synthase kinase-3beta inhibitor, TDZD-8, affects transient cerebral ischemia/reperfusion injury in the rat hippocampus. Collino M, Thiemermann C, Mastrocola R, Gallicchio M, Benetti E, Miglio G, Castiglia S, Danni O, Murch O, Dianzani C, Aragno M, Fantozzi R.Shock. 2008 Sep;30(3):299-307. doi: 10.1097/SHK.0b013e318164e762. PMID: 18323734 </br>6: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). Guzman ML, Li X, Corbett CA, Rossi RM, Bushnell T, Liesveld JL, Hébert J, Young F, Jordan CT.Blood. 2007 Dec 15;110(13):4436-44. Epub 2007 Sep 4. PMID: 17785584 Free PMC Article</br>7:What do insulin, estrogen, valproic acid, and TDZD-8 have in common? Fink MP.Crit Care Med. 2005 Sep;33(9):2115-7. No abstract available. PMID: 16148489 |
