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Biological Activity for DAPT
DAPT is a γ-secretase inhibitor. DAPT reduces Aβ40 and Aβ42 levels in human primary neuronal cultures (IC50 values are 115 and 200 nM for total Aβ and Aβ42 respectively) and in brain extract, cerebrospinal fluid and plasma in vivo. DAPT has no effect on APPα and APPβ levels. DAPT blocks Notch signaling in hybrid human-mouse fetal thymus organ culture (FTOC) and causes ESCs to commit to neuronal differentiation. DAPT can be used in a small molecule cocktail to derive cortical neurons from hPSCs and to maintain hepatocytes in culture. DAPT also promotes the formation of cone photoreceptors in retinal organoids.
DAPT synthesized to Ancillary Material Grade also available.
Applications in hiPSCs for DAPT
Dopaminergic Neurons Derived from hiPSCs using DAPT
Dopaminergic neurons derived from human induced pluripotent stem cells (hiPSC) using SB 431542 (Cat. No. 1614), CHIR 99021 (Cat. No. 4423), DAPT and Purmorphamine (Cat. No. 4551). Cells cultured in Neuronal Media supplemented with TGF-3 (Cat. No. 8420-B3, R&D Systems), cAMP, GDNF (Cat. No. 212-GD, R&D Systems), BDNF (Cat. No. 248-BDB, R&D Systems), N21-MAX (Cat. No. AR008, R&D Systems). Differentiation shown at days 55 (left) and 62 (right). Images courtesy of Kevin Flynn, Bio-Techne.
Compound Libraries for DAPT
Technical Data for DAPT
|Storage||Store at +4°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.
Solubility Data for DAPT
|Solvent||Max Conc. mg/mL||Max Conc. mM|
Preparing Stock Solutions for DAPT
The following data is based on the product molecular weight 432.46. 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||2.31 mL||11.56 mL||23.12 mL|
|5 mM||0.46 mL||2.31 mL||4.62 mL|
|10 mM||0.23 mL||1.16 mL||2.31 mL|
|50 mM||0.05 mL||0.23 mL||0.46 mL|
References for DAPT
References are publications that support the biological activity of the product.
Dovey et al (2001) Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J.Neurochem. 76 173 PMID: 11145990
De Smedt et al (2005) Different thresholds of notch signaling bias human precursor cells towards B-, NK-, monocytic/dendritic, or T-cell lineage in thymus microenvironment. Blood 106 3498 PMID: 16030192
Crawford and Roelink (2007) The notch response inhibitor DAPT enhances neuronal differentiation in embryonic stem cell-derived embryoid bodies independently of sonic hedgehog signaling. Dev.Dyn. 236 886 PMID: 17295317
Sato et al (2015) Snapshot: growing organoids from stem cells. Cell 161 1700 PMID: 26091044
Qi et al (2017) Combined small-molecule inhibition accelerates the derivation of functional cortical neurons from human pluripotent stem cells. Nat.Biotechnol. 35 153 PMID: 28112759
Xiang et al (2019) Long-term functional maintenance of primary human hepatocytes in vitro. Science 364 399 PMID: 31023926
Zerti et al (2020) Developing a simple method to enhance the generation of cone and rod photoreceptors in pluripotent stem cell-derived retinal organoids. Stem Cells 38 45 PMID: 31670434
If you know of a relevant reference for DAPT, please let us know.
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53 Citations for DAPT
Citations are publications that use Tocris products. Selected citations for DAPT include:
Kim et al (2021) Biphasic activation of WNT signaling facilitates the derivation of midbrain dopamine neurons from hESCs for translational use. Cell Stem Cell 28 343 PMID: 33545081
Piao et al (2021) Preclinical Efficacy and Safety of a Human Embryonic Stem Cell-Derived Midbrain Dopamine Progenitor Product, MSK-DA01 Cell Stem Cell 28 217 PMID: 33545080
Yang et al (2020) A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids Cell Stem Cell 27 125 PMID: 32579880
Fraser et al (2013) Common developmental pathways link tooth shape to regeneration. Dev Biol 377 399 PMID: 23422830
Li et al (2013) Shaping organs by a wingless-int/Notch/nonmuscle myosin module which orients feather bud elongation. Proc Natl Acad Sci U S A 110 E1452 PMID: 23576731
Campos et al (2012) Opposing effects of bacitracin on human papillomavirus type 16 infection: enhancement of binding and entry and inhibition of endosomal penetration. J Virol 86 4169 PMID: 22345461
Boulter et al (2012) Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Nat Med 18 572 PMID: 22388089
Hu et al (2012) Fibulin-3 promotes glioma growth and resistance through a novel paracrine regulation of Notch signaling. Cancer Res 72 3873 PMID: 22665268
Bejjani and Hammarlund (2012) Notch signaling inhibits axon regeneration. PLoS One 73 268 PMID: 22284182
Haidar et al (2019) Neuropathy-causing mutations in HSPB1 impair autophagy by disturbing the formation of SQSTM1/p62 bodies. Autophagy 15 1051 PMID: 30669930
Wang (2018) Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector. Nat Med 24 647 PMID: 29632371
Calton et al (2017) Translocation of the papillomavirus L2/vDNA complex across the limiting membrane requires the onset of mitosis. PLoS Pathog 13 e1006200 PMID: 28463988
Raven et al (2017) Soluble Gamma-secretase Modulators Attenuate Alzheimer's β-amyloid Pathology and Induce Conformational Changes in Presenilin 1. EBioMedicine 24 93 PMID: 28919280
Schumacher (2017) ErbB4 signaling stimulates pro-inflammatory macrophage apoptosis and limits colonic inflammation. Cell Death Dis 8 e2622 PMID: 28230865
Marumo et al (2013) Notch signaling regulates nucleocytoplasmic Olig2 translocation in reactive astrocytes differentiation after ischemic stroke. Neurosci Res 75 204 PMID: 23396245
Díaz et al (2013) Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia. J Cell Biol 201 279 PMID: 23589494
Du et al (2013) Inflammation-mediated notch signaling skews fanconi anemia hematopoietic stem cell differentiation. J Immunol 191 2806 PMID: 23926327
Kirkeby et al (2013) Generating regionalized neuronal cells from pluripotency, a step-by-step protocol. Front Cell Neurosci 6 64 PMID: 23316134
Sundvik et al (2013) Presenilin1 regulates histamine neuron development and behavior in zebrafish, danio rerio. J Neurosci 33 1589 PMID: 23345232
Hsieh and Lo (2012) Jagged1 and Notch1 help edit M cell patterning in Peyer's patch follicle epithelium. Dev Comp Immunol 37 306 PMID: 22504165
Tchieu et al (2017) A modular platform for differentiation of human PSCs into all major ectodermal lineages. Cell Stem Cell 21 399 PMID: 28886367
Alsanie (2017) Specification of murine ground state pluripotent stem cells to regional neuronal populations. Sci Rep 7 16001 PMID: 29167563
Xiang et al (2019) Long-term functional maintenance of primary human hepatocytes in vitro. Science 364 399 PMID: 31023926
Pitt et al (2017) Neuroprotective astrocyte-derived Ins/IGF-1 stimulates endocytic processing and extracellular release of neuron-bound Aβ oligomers. Mol Biol Cell 28 2623 PMID: 28963439
Kerr et al (2015) A small molecule targeting ALK1 prevents Notch cooperativity and inhibits functional angiogenesis. Angiogenesis 18 209 PMID: 25557927
Wang et al (2015) Generation of clinical-grade human induced pluripotent stem cells in Xeno-free conditions. Stem Cell Res Ther 6 223 PMID: 26564165
Edri et al (2015) Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors. Nat Commun 6 6500 PMID: 25799239
Gioia et al (2014) Mir-23a and mir-125b regulate neural stem/progenitor cell proliferation by targeting Musashi1. Anticancer Res 11 1105 PMID: 25483045
Shah et al (2013) The role of Notch and γ-secretase inhibition in an ovarian cancer model. J Neurosci 33 801 PMID: 23482747
Berndt et al (2011) Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/β-catenin signaling. J Cell Biol 194 737 PMID: 21875946
Kolegraff et al (2011) Characterization of full-length and proteolytic cleavage fragments of desmoglein-2 in native human colon and colonic epithelial cell lines. Cell Adh Migr 5 306 PMID: 21715983
Vila et al (2019) Quantification of human neuromuscular function through optogenetics. Theranostics 9 1232 PMID: 30867827
Lin et al (2017) Lactate-activated macrophages induced aerobic glycolysis and epithelial-mesenchymal transition in breast cancer by regulation of CCL5-CCR5 axis: a positive metabolic feedback loop. Oncotarget 8 110426 PMID: 29299159
Wang et al (2018) The COPII cargo adapter SEC24C is essential for neuronal homeostasis. J Clin Invest 128 3319 PMID: 29939162
Takeuchi et al (2018) VGF nerve growth factor inducible is involved in retinal ganglion cells death induced by optic nerve crush. Sci Rep 8 16443 PMID: 30401804
Sheng et al (2018) A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation. Nat Commun 9 4047 PMID: 30279449
Kishinevsky et al (2018) HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain DA neurons. Nat Commun 9 4345 PMID: 30341316
Greife et al (2014) Canonical Notch signalling is inactive in urothelial carcinoma. BMC Cancer 14 628 PMID: 25167871
Hammond et al (2014) Astrocyte-derived endothelin-1 inhibits remyelination through notch activation. Neuron 81 588 PMID: 24507193
Campbell et al (2016) Canonical Notch signaling plays an instructive role in auditory supporting cell development. Zoological Lett 6 19484 PMID: 26786414
Lu et al (2016) Generation of serotonin neurons from human pluripotent stem cells. Nat Biotechnol 34 89 PMID: 26655496
Wang et al (2016) Efficient Generation of Hypothalamic Neurons from Human Pluripotent Stem Cells. Curr Protoc Hum Genet 90 21.5.1 PMID: 27367166
Zeltner et al (2016) Capturing the biology of disease severity in a PSC-based model of familial dysautonomia. Nat Med 22 1421 PMID: 27841875
Onai et al (2015) On the origin of vertebrate somites. Blood 1 33 PMID: 26613046
Gomez et al (2015) Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate. Sci Rep 10 e0133862 PMID: 26288179
Scheppke et al (2012) Notch promotes vascular maturation by inducing integrin-mediated smooth muscle cell adhesion to the endothelial basement membrane. Cell Stem Cell 119 2149 PMID: 22134168
Valdez et al (2012) Notch and TGFβ form a reciprocal positive regulatory loop that suppresses murine prostate basal stem/progenitor cell activity. RNA Biol 11 676 PMID: 23122291
Kim et al (2010) Group II metabotropic glutamate receptor stimulation triggers production and release of Alzheimer's amyloid(β)42 from isolated intact nerve terminals. Neuron 30 3870 PMID: 20237257
Yang (2018) A biodegradable hybrid inorganic nanoscaffold for advanced stem cell therapy. Nat Commun 9 3147 PMID: 30089775
Ikram et al (2018) Co-targeting of Tiam1/Rac1 and Notch ameliorates chemoresistance against dox. in a biomimetic 3D lymphoma model. Oncotarget 9 2058 PMID: 29416753
Gibb et al (2018) Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development. Development 145 PMID: 30355727
Guest et al (2016) Notch3 drives development and progression of cholangiocarcinoma Proc Natl Acad Sci U S A. 113 12250 PMID: 27791012
Pavlou et al (2014) Pleiotropic effects of Sox2 during the development of the zebrafish epithalamus. PLoS One 9 e87546 PMID: 24498133
Do you know of a great paper that uses DAPT from Tocris? Please let us know.
Reviews for DAPT
Average Rating: 4.8 (Based on 6 Reviews.)
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For hPSC culture, final concentration 10 μM DAPT.
Make 100µl aliquots and keep them at −20 °C for up to 6 months.
gamma -secretase (100 nM BMS 299897 and 250 nM DAPT)
Used successfully for the differentiation of iPSCs into dopaminergic neurons.
Solubilised in DMSO.
In cell line culture of human cells
I used this product for differentiation of iPSCs into dopaminergic neurons according to the protocol published in Kriks et al, 2011.I used the concentration 10uM and it works really well.
Protocols for DAPT
The following protocols feature additional information for the use of DAPT (Cat. No. 2634).
Literature in this Area
Tocris offers the following scientific literature in this area to showcase our products. We invite you to request* your copy today!
*Please note that Tocris will only send literature to established scientific business / institute addresses.
Stem Cells Scientific Review
Written by Kirsty E. Clarke, Victoria B. Christie, Andy Whiting and Stefan A. Przyborski, this review provides an overview of the use of small molecules in the control of stem cell growth and differentiation. Key signaling pathways are highlighted, and the regulation of ES cell self-renewal and somatic cell reprogramming is discussed. Compounds available from Tocris are listed.
Huntington's Disease Poster
Huntington's disease (HD) is a monogenic neurodegenerative disorder, which is characterized by the prevalent loss of GABAergic medium spiny neurons (MSN) in the striatum. This poster summarizes the MSN intracellular signaling pathways implicated in the pathology of HD, as well as highlighting the use of iPSCs for HD modeling.
Parkinson's disease (PD) causes chronic disability and is the second most common neurodegenerative condition. This poster outlines the neurobiology of the disease, as well as highlighting current therapeutic treatments for symptomatic PD, and emerging therapeutic strategies to delay PD onset and progression.
Stem Cell Workflow Poster
Stem cells have potential as a source of cells and tissues for research and treatment of disease. This poster summarizes some key protocols demonstrating the use of small molecules across the stem cell workflow, from reprogramming, through self-renewal, storage and differentiation to verification. Advantages of using small molecules are also highlighted.