WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H406208
CAS#: 327036-89-5
Description: TDZD-8 is a serine/threonine glycogen synthase kinase 3beta (GSK-3beta) inhibitor. GSK-3beta is abundant in the central nervous system, particularly in the hippocampus, and plays a pivotal role in the pathophysiology of a number of diseases, including neurodegeneration. TDZD-8 protects the brain against I/R injury by inhibiting GSK-3beta activity. TDZD-8 decreased proliferation and induced apoptosis of GL261 glioblastoma cells in vitro, delayed tumor growth in vivo, and augmented animal survival. These effects were associated with an early activation of extracellular signal-regulated kinase (ERK) pathway and increased expression of EGR-1 and p21 genes.
Hodoodo Cat#: H406208
Name: TDZD-8
CAS#: 327036-89-5
Chemical Formula: C10H10N2O2S
Exact Mass: 222.05
Molecular Weight: 222.260
Elemental Analysis: C, 54.04; H, 4.53; N, 12.60; O, 14.40; S, 14.43
Synonym: TDZD8; TDZD-8; TDZD 8. GSK3 Inhibitor I; NP 01139; NP-01139; NP01139.
IUPAC/Chemical Name: 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione
InChi Key: JDSJDASOXWCHPN-UHFFFAOYSA-N
InChi Code: InChI=1S/C10H10N2O2S/c1-11-9(13)12(10(14)15-11)7-8-5-3-2-4-6-8/h2-6H,7H2,1H3
SMILES Code: O=C(N1CC2=CC=CC=C2)N(C)SC1=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | TDZD-8 is an inhibitor of GSK-3β with an IC50 of 2 μM. |
| In vitro activity: | The antiproliferative effect of TDZD-8 on GL261 glioblastoma cells was tested analyzing BrdU incorporation. Exponentially growing GL261 cells were exposed to 20 µM TDZD-8 for 24 and 48 h, and their proliferation was monitored. A significant decrease in proliferation was observed in cells treated for both 24 and 48 h with 20 µM TDZD-8 compared with untreated control cells (Fig. 3A). Additionally, cell viability, measured by the MTT assay, was significantly diminished in TDZD-8-treated cells (Fig. 3B), compared to controls. Thus, TDZD-8 has an antiproliferative effect on GL261 glioblastoma cells. This anti-proliferative effect of TDZD-8 was also observed in other two human glioblastoma cell lines, A172 (Fig. 3C, D) and U373 (Fig. 3E, F). Reference: PLoS One. 2010 Nov 8;5(11):e13879. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2975629/ |
| In vivo activity: | Whether TDZD-8 can lead to improved sensorimotor function was investigated using a hypoxic-ischemic (HI) model in neonatal mice. Seven days after HI, the neurobehavioral function of mice was assessed using the cliff avoidance test. The vehicle control group (7 days: 6.14±1.63 seconds) displayed a significantly longer latency to complete the test in comparison with the sham group (7 days: 2.03±0.15 seconds). TDZD-8 pretreatment (7 days: 3.02±0.45 seconds) significantly reduced the latency to complete the test in comparison with the vehicle group (Figure 3A, *P<.05). These results indicated that TDZD-8 improves the locomotion and reduces maladaptive behavior response of the mice following HI. Reference: CNS Neurosci Ther. 2017 May;23(5):405-415. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492674/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 20.0 | 89.98 | |
| DMSO | 46.7 | 210.02 | |
| Ethanol | 28.9 | 130.07 |
The following data is based on the product molecular weight 222.26 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Aguilar-Morante D, Morales-Garcia JA, Sanz-SanCristobal M, Garcia-Cabezas MA, Santos A, Perez-Castillo A. Inhibition of glioblastoma growth by the thiadiazolidinone compound TDZD-8. PLoS One. 2010 Nov 8;5(11):e13879. doi: 10.1371/journal.pone.0013879. PMID: 21079728; PMCID: PMC2975629. 2. Guzman ML, Li X, Corbett CA, Rossi RM, Bushnell T, Liesveld JL, Hébert J, Young F, Jordan CT. 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 Dec 15;110(13):4436-44. doi: 10.1182/blood-2007-05-088815. Epub 2007 Sep 4. PMID: 17785584; PMCID: PMC2234782. 3. Huang S, Wang H, Turlova E, Abussaud A, Ji X, Britto LR, Miller SP, Martinez A, Sun HS, Feng ZP. GSK-3β inhibitor TDZD-8 reduces neonatal hypoxic-ischemic brain injury in mice. CNS Neurosci Ther. 2017 May;23(5):405-415. doi: 10.1111/cns.12683. Epub 2017 Mar 2. PMID: 28256059; PMCID: PMC6492674. 4. Koehler D, Shah ZA, Williams FE. The GSK3β inhibitor, TDZD-8, rescues cognition in a zebrafish model of okadaic acid-induced Alzheimer's disease. Neurochem Int. 2019 Jan;122:31-37. doi: 10.1016/j.neuint.2018.10.022. Epub 2018 Oct 28. PMID: 30392874. |
| In vitro protocol: | 1. Aguilar-Morante D, Morales-Garcia JA, Sanz-SanCristobal M, Garcia-Cabezas MA, Santos A, Perez-Castillo A. Inhibition of glioblastoma growth by the thiadiazolidinone compound TDZD-8. PLoS One. 2010 Nov 8;5(11):e13879. doi: 10.1371/journal.pone.0013879. PMID: 21079728; PMCID: PMC2975629. 2. Guzman ML, Li X, Corbett CA, Rossi RM, Bushnell T, Liesveld JL, Hébert J, Young F, Jordan CT. 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 Dec 15;110(13):4436-44. doi: 10.1182/blood-2007-05-088815. Epub 2007 Sep 4. PMID: 17785584; PMCID: PMC2234782. |
| In vivo protocol: | 1. Huang S, Wang H, Turlova E, Abussaud A, Ji X, Britto LR, Miller SP, Martinez A, Sun HS, Feng ZP. GSK-3β inhibitor TDZD-8 reduces neonatal hypoxic-ischemic brain injury in mice. CNS Neurosci Ther. 2017 May;23(5):405-415. doi: 10.1111/cns.12683. Epub 2017 Mar 2. PMID: 28256059; PMCID: PMC6492674. 2. Koehler D, Shah ZA, Williams FE. The GSK3β inhibitor, TDZD-8, rescues cognition in a zebrafish model of okadaic acid-induced Alzheimer's disease. Neurochem Int. 2019 Jan;122:31-37. doi: 10.1016/j.neuint.2018.10.022. Epub 2018 Oct 28. PMID: 30392874. |
1: Ansaldi D, Hod EA, Stellari F, Kim JB, Lim E, Roskey M, Francis KP, Singh R, Zhang N. Imaging pulmonary NF-kappaB activation and therapeutic effects of MLN120B and TDZD-8. PLoS One. 2011;6(9):e25093. doi: 10.1371/journal.pone.0025093. Epub 2011 Sep 22. PubMed PMID: 21966423; PubMed Central PMCID: PMC3178604.
2: Aguilar-Morante D, Morales-Garcia JA, Sanz-SanCristobal M, Garcia-Cabezas MA, Santos A, Perez-Castillo A. Inhibition of glioblastoma growth by the thiadiazolidinone compound TDZD-8. PLoS One. 2010 Nov 8;5(11):e13879. doi: 10.1371/journal.pone.0013879. PubMed PMID: 21079728; PubMed Central PMCID: PMC2975629.
3: Collino M, Thiemermann C, Mastrocola R, Gallicchio M, Benetti E, Miglio G, Castiglia S, Danni O, Murch O, Dianzani C, Aragno M, Fantozzi R. Treatment with the glycogen synthase kinase-3beta inhibitor, TDZD-8, affects transient cerebral ischemia/reperfusion injury in the rat hippocampus. Shock. 2008 Sep;30(3):299-307. doi: 10.1097/SHK.0b013e318164e762. PubMed PMID: 18323734.
4: Guzman ML, Li X, Corbett CA, Rossi RM, Bushnell T, Liesveld JL, Hébert J, Young F, Jordan CT. 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 Dec 15;110(13):4436-44. Epub 2007 Sep 4. PubMed PMID: 17785584; PubMed Central PMCID: PMC2234782.
5: Fink MP. What do insulin, estrogen, valproic acid, and TDZD-8 have in common? Crit Care Med. 2005 Sep;33(9):2115-7. PubMed PMID: 16148489.
