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Potent and highly selective inhibitor of glycogen synthase kinase 3 (GSK-3) (IC50 values are 6.7 and 10 nM for GSK-3β and GSK-3α respectively). Exhibits >500-fold selectivity for GSK-3 over closely related kinases; also displays >800-fold selectivity against 45 additional enzymes and receptors. In combination with tranylcypromine (Cat. No. 3852), enables reprogramming of mouse embryonic fibroblasts, transduced by Oct4 and Klf4 only, into iPSCs. Enhances mouse and human ESC self-renewal when used in combination with PD 0325901 (Cat. No. 4192). Allows formation of extended pluripotent stem (EPS) cells in combination with (S)-(+)-Dimethindene maleate (Cat.No. 1425), minocycline hydrochloride (Cat.No. 3268) and human leukemia inhibitory factor.
CHIR 99021 synthesized to cGMP guidelines also available.
|Storage||Store at -20°C|
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
|Solvent||Max Conc. mg/mL||Max Conc. mM|
Preparing Stock Solutions
The following data is based on the product molecular weight 465.34. 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|
|0.2 mM||10.74 mL||53.72 mL||107.45 mL|
|1 mM||2.15 mL||10.74 mL||21.49 mL|
|2 mM||1.07 mL||5.37 mL||10.74 mL|
|10 mM||0.21 mL||1.07 mL||2.15 mL|
References are publications that support the biological activity of the product.
Pan et al (2011) AKT kinase activity is required for Li to modulate mood-related behaviors in mice. Neuropsychopharmacology 36 1397 PMID: 21389981
Ring et al (2003) Selective glycogen synthase kinase 3 inhibitors potentiate Ins activation of glucose transport and utilization in vitro and in vivo. Diabetes 52 588 PMID: 12606497
Li et al (2009) Generation of human-induced pluripotent stem cells in the absence of exogenous Sox2. Stem Cells 27 2992 PMID: 19839055
Ye et al (2012) Pleiotropy of glycogen synthase kinase-3 inhibition by CHIR99021 promotes self-renewal of embyronic stem cells from refractory mouse strains. PLoS One 7 e35892 PMID: 22540008
Yang et al (2017) Derivation of pluripotent stem cells with in vivo embryonic and extraembryonic potency. Cell. 169 243 PMID: 28388409
If you know of a relevant reference for CHIR 99021, please let us know.
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Keywords: CHIR 99021, CHIR 99021 supplier, CHIR99021, glycogen, synthase, kinase, 3, gsk-3, gsk-3a, gsk-3alpha, gsk-3α, gsk-3b, gsk-3beta, gsk-3β, inhibitors, inhibits, highly, selective, potent, organoids, Glycogen, Synthase, Kinase, Reprogramming, 4423, Tocris Bioscience
53 Citations for CHIR 99021
Citations are publications that use Tocris products. Selected citations for CHIR 99021 include:
Yin et al (2019) Chemical conversion of human fetal astrocytes into neurons through modulation of multiple signaling pathways. Stem Cell Reports 12 488 PMID: 30745031
Sommer et al (2018) Th17 lymphocytes induce neuronal cell death in a human iPSC-based model of Parkinson's disease. Cell Stem Cell 23 123 PMID: 29979986
Liu et al (2018) CRISPR-based chromatin remodeling of the endogenous Oct4 or Sox2 locus enables reprogramming to pluripotency. Cell Stem Cell. 22 252 PMID: 29358044
Bantounas et al (2018) Generation of functioning nephrons by implanting human pluripotent stem cell-derived kidney progenitors. Stem Cell Reports 10 766 PMID: 29429961
Bar-Nur et al (2018) Direct reprogramming of mouse fibroblasts into functional skeletal muscle progenitors. Stem Cell Reports 10 1505 PMID: 29742392
Solari et al (2015) Manganese Superoxide Dismutase Gene Expression Is Induced by Nanog and Oct4, Essential Pluripotent Stem Cells' Transcription Factors. Mol Syst Biol 10 e0144336 PMID: 26642061
Mutze et al (2015) Enolase 1 (ENO1) and protein disulfide-isomerase associated 3 (PDIA3) regulate Wnt/β-catenin-driven trans-differentiation of murine alveolar epithelial cells. Cell Rep 8 877 PMID: 26035385
Srikanth et al (2015) Genomic DISC1 Disruption in hiPSCs Alters Wnt Signaling and Neural Cell Fate. Sci Rep 12 1414 PMID: 26299970
Morizane et al (2015) Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Stem Cell Reports 33 1193 PMID: 26458176
Nostro et al (2015) Efficient generation of NKX6-1+ pancreatic progenitors from multiple human pluripotent stem cell lines. Eur J Immunol 4 591 PMID: 25843049
Hill et al (2015) Glycogen synthase kinase-3 controls IL-10 expression in CD4(+) effector T-cell subsets through epigenetic modification of the IL-10 promoter. Mol Neurobiol 45 1103 PMID: 25627813
Ooi et al (2015) Inhibition of Excessive Monoamine Oxidase A/B Activity Protects Against Stress-induced Neuronal Death in Huntington Disease. Nat Chem Biol 52 1850 PMID: 25398695
Thorne et al (2015) GSK-3 modulates cellular responses to a broad spectrum of kinase inhibitors. Mol Biol Cell 11 58 PMID: 25402767
Barbosa et al (2015) Phosphorylation and SCF-mediated degradation regulate CREB-H transcription of metabolic targets. Stem Cell Reports 26 2939 PMID: 26108621
Muthusamy et al (2014) A method to identify and isolate pluripotent human stem cells and mouse epiblast stem cells using lipid body-associated retinyl ester fluorescence. Stem Cell Reports 3 169 PMID: 25068130
Zhu et al (2014) Mouse liver repopulation with hepatocytes generated from human fibroblasts. Nature 508 93 PMID: 24572354
Christoforou et al (2017) Core Transcription Factors, MicroRNAs, and Small Molecules Drive Transdifferentiation of Human Fibroblasts Towards The Cardiac Cell Lineage. Sci Rep 7 40285 PMID: 28071742
Zhao et al (2017) Efficient differentiation of TBX18(+)/WT1(+) epicardial-like cells from human pluripotent stem cells using small molecular compounds. Stem Cells Dev 26 528 PMID: 27927069
Du et al (2015) Generation and expansion of highly pure motor neuron progenitors from human pluripotent stem cells. Nat.Commun. 6 6626 PMID: 25806427
Sladitschek and Neveu (2015) The bimodally expressed microRNA miR-142 gates exit from pluripotency. J Biol Chem 11 850 PMID: 26690966
Hugo et al (2015) Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance. Cell 162 1271 PMID: 26359985
Yang (2017) Mutual reinforcement between telomere capping and canonical Wnt signalling in the intestinalstem cell niche. Nat Commun 8 14766 PMID: 28303901
Yang et al (2017) Derivation of pluripotent stem cells with in vivo embryonic and extraembryonic potency. Cell. 169 243 PMID: 28388409
Xi (2017) In Vivo Human Somitogenesis Guides Somite Development from hPSCs. Cell Rep. 18 1573 PMID: 28178531
Kotton et al (2017) Differentiation of human pluripotent stem cells into functional lung alveolar epithelial cells. Cell Stem Cell. 21 472 PMID: 28965766
Tchieu et al (2017) A modular platform for differentiation of human PSCs into all major ectodermal lineages. Cell Stem Cell. 21 399 PMID: 28886367
Shao (2017) A pluripotent stem cell-based model for post-implantation human amniotic sac development. Nat Commun 8 208 PMID: 28785084
Brown (2017) Live imaging reveals that the first division of differentiating human embryonic stem cells often yields asymmetric fates. Cell Rep 21 301 PMID: 29020617
Zhang et al (2016) Pharmacological reprogramming of fibroblasts into neural stem cells by signaling-directed transcriptional activation. Cell Stem Cell 18 653 PMID: 27133794
Mou et al (2016) Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells Cell: Stem Cell 19 217 PMID: 27320041
Lu et al (2016) Generation of serotonin neurons from human pluripotent stem cells. Nat Biotechnol 34 89 PMID: 26655496
Chal et al (2016) Generation of human muscle fibers and satellite-like cells from human pluripotent stem cells in vitro. Nat.Protoc. 11 1833 PMID: 27583644
Woo et al (2016) Enhancing a Wnt-Telomere Feedback Loop Restores Intestinal Stem Cell Function in a Human Organotypic Model of Dyskeratosis Congenita Cell Stem Cell 19 397 PMID: 27545506
Takasato et al (2016) Generation of kidney organoids from human pluripotent stem cells. Nature Protocols 11 1681 PMID: 27560173
Shelton et al (2014) Derivation and expansion of PAX7-positive muscle progenitors from human and mouse embryonic stem cells. Dis Model Mech 3 516 PMID: 25241748
Wu et al (2014) A novel suppressive effect of alcohol dehydrogenase 5 in neuronal differentiation. Stem Cell Res 289 20193 PMID: 24895131
Skelton et al (2014) SIRPA, VCAM1 and CD34 identify discrete lineages during early human cardiovascular development. J Cachexia Sarcopenia Muscle 13 172 PMID: 24968096
Foulke-Abel et al (2016) Human Enteroids as a Model of Upper Small Intestinal Ion Transport Physiology and Pathophysiology. Nat Commun 150 638 PMID: 26677983
Long et al (2016) Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin. Nat Biotechnol 7 10354 PMID: 26838601
Huang et al (2016) Generating trunk neural crest from human pluripotent stem cells. PLoS One 6 19727 PMID: 26812940
Leung et al (2016) WNT/β-catenin signaling mediates human neural crest induction via a pre-neural border intermediate. Development 143 398 PMID: 26839343
Chesnokova et al (2016) GH is permissive for neoplastic colon growth. Proc Natl Acad Sci U S A 113 E3250 PMID: 27226307
Nakaoka et al (2016) Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus. PLoS Genet 12 e1005893 PMID: 27055116
Fattahi et al (2016) Deriving human ENS lineages for cell therapy and drug discovery in Hirschsprung disease. Nature 531 105 PMID: 26863197
Zhang et al (2015) Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons. Cell Stem Cell 17 735 PMID: 26481520
Watmuff et al (2015) Human pluripotent stem cell derived midbrain PITX3(eGFP/w) neurons: a versatile tool for pharmacological screening and neurodegenerative modeling. Front Cell Neurosci 9 104 PMID: 25873861
Zhang et al (2015) GSK3β-Dzip1-Rab8 cascade regulates ciliogenesis after mitosis. PLoS Biol 13 e1002129 PMID: 25860027
Francipane and Lagasse (2015) The lymph node as a new site for kidney organogenesis. Stem Cells Transl Med 4 295 PMID: 25646529
Kearns et al (2015) Functional annotation of native enhancers with a Cas9-histone demethylase fusion. Nat Methods 12 401 PMID: 25775043
Jain et al (2015) Plasticity of Hopx(+) type I alveolar cells to regenerate type II cells in the lung. Nat Commun 6 6727 PMID: 25865356
Huebsch et al (2015) Automated Video-Based Analysis of Contractility and Calcium Flux in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Cultured over Different Spatial Scales. Tissue Eng Part C Methods 21 467 PMID: 25333967
Orlova et al (2014) Functionality of endothelial cells and pericytes from human pluripotent stem cells demonstrated in cultured vascular plexus and zebrafish xenografts. Arterioscler Thromb Vasc Biol 34 177 PMID: 24158517
Naujok et al (2014) Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors. BMC Res Notes 7 273 PMID: 24779365
Do you know of a great paper that uses CHIR 99021 from Tocris? Please let us know.
Reviews for CHIR 99021
Average Rating: 4.7 (Based on 3 Reviews.)
Have you used CHIR 99021?
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Culture mouse ES cells in 2i media and without 2i to assess differentiation. Only the cells in 2i are pluripotent while mES cells cultured in -2i for 48 hours exit naive pluripotency.
For directed differentiation of pluripotent stem cells to kidney organoids, cells are treated with GSK-3 inhibitor, CHIR99021 to induce canonical WNT signaling. CHIR99021 concentration and differentiation time period are the key factors for this protocol. I found this product gave me reproducible results.
Although the datasheet says store at -20°C, it's better to aliquot and keep it at -80°C for long term storage.
Protocols for CHIR 99021
The following protocols feature additional information for the use of CHIR 99021 (Cat. No. 4423).
- Transdifferentiating Fibroblasts into Neurons
- Culturing Transcriptomically Distinct Pluripotent mESCs
- Converting Fibroblasts into Cardiomyocytes (9C Cocktail)
- Human iPSC-derived Myoblasts
- Generation of Kidney Organoids from hPSCs
- Reprogramming MEFs into Skeletal Muscle Progenitors
- Highly Efficient Generation of CiPSCs from MEFs
- Generation of β cells from hPSCs
- Generation and Propagation of EPS cells (LCDM Cocktail)
Literature in this Area
Tocris offers the following scientific literature in this area to showcase our products. We invite you to request* or download your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
Alzheimer's disease (AD) is a degenerative brain disease and the most common cause of dementia, affecting approximately 47 million people worldwide. Updated in 2015, this poster summarizes the structural and functional changes observed in the progression of this neurodegenerative disease, as well as classic AD drug targets.
Schizophrenia is a debilitating psychiatric disorder that affects 1% of the worldwide population. This poster describes the neurobiology of Schizophrenia, as well as highlighting the genetic and environmental factors that play a fundamental role in the etiology of the disease. The current and emerging drug targets are also discussed.