TDZD-8 | NP-01139 |CAS#327036-89-5 | GSK inhibitor

MedKoo Cat#: 406208 | Name: TDZD-8

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

TDZD-8

CAS#327036-89-5

Theoretical Analysis

MedKoo Cat#: 406208

Name: TDZD-8

CAS#: 327036-89-5

Chemical Formula: C10H10N2O2S

Exact Mass: 222.0463

Molecular Weight: 222.26

Elemental Analysis: C, 54.04; H, 4.53; N, 12.60; O, 14.40; S, 14.43

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to Ship
10mg	USD 150.00	Ready to Ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
1g	USD 4,250.00	2 weeks

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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

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot# TZC41015

QC Data

View QC data, current batch, Lot#TZC41015

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMF	20.0	89.98
	DMSO	46.7	210.02
	Ethanol	28.9	130.07

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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:

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.

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PMID: 38033124; PMCID: PMC10688887. 4: Kakraba S, Ayyadevara S, Mainali N, Balasubramaniam M, Bowroju S, Penthala NR, Atluri R, Barger SW, Griffin ST, Crooks PA, Shmookler Reis RJ. Thiadiazolidinone (TDZD) Analogs Inhibit Aggregation-Mediated Pathology in Diverse Neurodegeneration Models, and Extend C. elegans Life- and Healthspan. Pharmaceuticals (Basel). 2023 Oct 20;16(10):1498. doi: 10.3390/ph16101498. PMID: 37895969; PMCID: PMC10610358. 5: Yu H, Xiong M, Liu C, Xia D, Meng L, Zhang Z. The γ-Adducin 1-357 fragment promotes tau pathology. Front Aging Neurosci. 2023 Sep 13;15:1241750. doi: 10.3389/fnagi.2023.1241750. PMID: 37771520; PMCID: PMC10526357. 6: Al-Serwi RH, Othman G, Dawood AF, Alhumaidan AK, Alharbi HS, El-Sherbiny M, Almadani ME, Elsherbini DMA. Impact of glycogen synthase kinase-3ß inhibition on rats' temporomandibular joint collagen-induced rheumatoid arthritis with correlation to miRNA-155/miRNA-24 expression. Eur Rev Med Pharmacol Sci. 2023 Aug;27(16):7416-7430. doi: 10.26355/eurrev_202308_33393. PMID: 37667918. 7: Zhang D, Shi C, Zhang Q, Wang Y, Guo J, Gong Z. Inhibition of GSK3β activity alleviates acute liver failure via suppressing multiple programmed cell death. J Inflamm (Lond). 2023 Jul 13;20(1):24. doi: 10.1186/s12950-023-00350-1. Erratum in: J Inflamm (Lond). 2024 Jun 12;21(1):21. doi: 10.1186/s12950-024-00390-1. PMID: 37443080; PMCID: PMC10347874. 8: Yang HY, Sun X, Zhen SQ, Yu LZ, Ding JQ, Liu L, Xie M, Zhu HL. GSK-3β inhibition alleviates arthritis pain via reducing spinal mitochondrial reactive oxygen species level and inflammation. PLoS One. 2023 Apr 14;18(4):e0284332. doi: 10.1371/journal.pone.0284332. PMID: 37058473; PMCID: PMC10104309. 9: Matsuno M, Yokoe S, Nagatsuka T, Morihara H, Moriwaki K, Asahi M. O-GlcNAcylation-induced GSK-3β activation deteriorates pressure overload- induced heart failure via lack of compensatory cardiac hypertrophy in mice. 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PMID: 36092604; PMCID: PMC9453980. 13: Yang HY, Zhang F, Cheng ML, Wu J, Xie M, Yu LZ, Liu L, Xiong J, Zhu HL. Glycogen synthase kinase-3β inhibition decreases inflammation and relieves cancer induced bone pain via reducing Drp1-mediated mitochondrial damage. J Cell Mol Med. 2022 Jul;26(14):3965-3976. doi: 10.1111/jcmm.17432. Epub 2022 Jun 10. PMID: 35689386; PMCID: PMC9279596. 14: Qin CQ, Huang B, Yang F, Wang CM, Xiao Y, Mo YJ, Liao Y, Gao F. [Effects of GSK3β/eEF2K signaling pathway on pulmonary fibrosis in mice]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Jan;38(1):32-36. Chinese. doi: 10.12047/j.cjap.6201.2022.006. PMID: 35634666. 15: Liu J, Li L, Xie P, Zhao X, Shi D, Zhang Y, Pan C, Li T. Sevoflurane induced neurotoxicity in neonatal mice links to a GSK3β/Drp1-dependent mitochondrial fission and apoptosis. Free Radic Biol Med. 2022 Mar;181:72-81. doi: 10.1016/j.freeradbiomed.2022.01.031. Epub 2022 Feb 2. PMID: 35122996. 16: Zou W, Ye D, Liu S, Hu J, Zhu T, He F, Ran P. GSK-3β Inhibitors Attenuate the PM2.5-Induced Inflammatory Response in Bronchial Epithelial Cells. Int J Chron Obstruct Pulmon Dis. 2021 Oct 14;16:2845-2856. doi: 10.2147/COPD.S327887. PMID: 34703220; PMCID: PMC8523522. 17: Berenguer E, Carneros E, Pérez-Pérez Y, Gil C, Martínez A, Testillano PS. Small molecule inhibitors of mammalian GSK-3β promote in vitro plant cell reprogramming and somatic embryogenesis in crop and forest species. J Exp Bot. 2021 Dec 4;72(22):7808-7825. doi: 10.1093/jxb/erab365. PMID: 34338766; PMCID: PMC8664590. 18: Liu Q, Kong Y, Guo X, Liang B, Xie H, Hu S, Han M, Zhao X, Feng P, Lyu Q, Dong W, Liang X, Wang W, Li C. GSK-3β inhibitor TDZD-8 prevents reduction of aquaporin-1 expression via activating autophagy under renal ischemia reperfusion injury. FASEB J. 2021 Aug;35(8):e21809. doi: 10.1096/fj.202100549R. PMID: 34314052. 19: Han S, Zhuang C, Zhou W, Chen F. 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