Chemical Name: (2S)-N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine 1,1-dimethylethyl ester
Biological ActivityDAPT 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.
Applications in hiPSCs
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.
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Tocris products are intended for laboratory research use only, unless stated otherwise.
The notch response inhibitor DAPT enhances neuronal differentiation in embryonic stem cell-derived embryoid bodies independently of sonic hedgehog signaling.
Crawford and Roelink
Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.
Dovey et al.
Different thresholds of notch signaling bias human precursor cells towards B-, NK-, monocytic/dendritic, or T-cell lineage in thymus microenvironment.
De Smedt et al.
SnapShot: Growing Organoids from Stem Cells.
Sato et al.
Citations for DAPT
The citations listed below are publications that use Tocris products. Selected citations for DAPT include:
51 Citations: Showing 1 - 10
A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids
Authors: Yang Et al.
Cell Stem Cell 2020;27:125
Quantification of human neuromuscular function through optogenetics.
Authors: Vila Et al.
Long-term functional maintenance of primary human hepatocytes in vitro.
Authors: Xiang Et al.
Neuropathy-causing mutations in HSPB1 impair autophagy by disturbing the formation of SQSTM1/p62 bodies.
Authors: Haidar Et al.
HSP90-incorporating chaperome networks as biosensor for disease-related pathways in patient-specific midbrain DA neurons.
Authors: Kishinevsky Et al.
Nat Commun 2018;9:4345
A stably self-renewing adult blood-derived induced neural stem cell exhibiting patternability and epigenetic rejuvenation.
Authors: Sheng Et al.
Nat Commun 2018;9:4047
A biodegradable hybrid inorganic nanoscaffold for advanced stem cell therapy.
Nat Commun 2018;9:3147
Co-targeting of Tiam1/Rac1 and Notch ameliorates chemoresistance against dox. in a biomimetic 3D lymphoma model.
Authors: Ikram Et al.
VGF nerve growth factor inducible is involved in retinal ganglion cells death induced by optic nerve crush.
Authors: Takeuchi Et al.
Sci Rep 2018;8:16443
Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector.
Nat Med 2018;24(5):647
Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development.
Authors: Gibb Et al.
The COPII cargo adapter SEC24C is essential for neuronal homeostasis.
Authors: Wang Et al.
J Clin Invest 2018;128:3319
ErbB4 signaling stimulates pro-inflammatory macrophage apoptosis and limits colonic inflammation.
Cell Death Dis 2017;8:e2622
Lactate-activated macrophages induced aerobic glycolysis and epithelial-mesenchymal transition in breast cancer by regulation of CCL5-CCR5 axis: a positive metabolic feedback loop.
Authors: Lin Et al.
Specification of murine ground state pluripotent stem cells to regional neuronal populations.
Sci Rep 2017;7(1):16001
Neuroprotective astrocyte-derived Ins/IGF-1 stimulates endocytic processing and extracellular release of neuron-bound Aβ oligomers.
Authors: Pitt Et al.
Mol Biol Cell 2017;28:2623
Soluble Gamma-secretase Modulators Attenuate Alzheimer's β-amyloid Pathology and Induce Conformational Changes in Presenilin 1.
Authors: Raven Et al.
A modular platform for differentiation of human PSCs into all major ectodermal lineages.
Authors: Tchieu Et al.
Cell Stem Cell 2017;21:399
Translocation of the papillomavirus L2/vDNA complex across the limiting membrane requires the onset of mitosis.
Authors: Calton Et al.
PLoS Pathog 2017;13:e1006200
Efficient Generation of Hypothalamic Neurons from Human Pluripotent Stem Cells.
Authors: Wang Et al.
Curr Protoc Hum Genet 2016;90:21.5.1
Canonical Notch signaling plays an instructive role in auditory supporting cell development.
Authors: Campbell Et al.
Zoological Lett 2016;6:19484
Generation of serotonin neurons from human pluripotent stem cells.
Authors: Lu Et al.
Nat Biotechnol 2016;34:89
Capturing the biology of disease severity in a PSC-based model of familial dysautonomia.
Authors: Zeltner Et al.
Nat Med 2016;22:1421
Notch3 drives development and progression of cholangiocarcinoma
Authors: Guest Et al.
Proc Natl Acad Sci U S A. 2016;113:12250
Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors.
Authors: Edri Et al.
Nat Commun 2015;6:6500
Generation of clinical-grade human induced pluripotent stem cells in Xeno-free conditions.
Authors: Wang Et al.
Stem Cell Res Ther 2015;6:223
On the origin of vertebrate somites.
Authors: Onai Et al.
A small molecule targeting ALK1 prevents Notch cooperativity and inhibits functional angiogenesis.
Authors: Kerr Et al.
Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate.
Authors: Gomez Et al.
Sci Rep 2015;10:e0133862
Pleiotropic effects of Sox2 during the development of the zebrafish epithalamus.
Authors: Pavlou Et al.
PLoS One 2014;9:e87546
Astrocyte-derived endothelin-1 inhibits remyelination through notch activation.
Authors: Hammond Et al.
Canonical Notch signalling is inactive in urothelial carcinoma.
Authors: Greife Et al.
BMC Cancer 2014;14:628
Mir-23a and mir-125b regulate neural stem/progenitor cell proliferation by targeting Musashi1.
Authors: Gioia Et al.
Anticancer Res 2014;11:1105
Notch signaling regulates nucleocytoplasmic Olig2 translocation in reactive astrocytes differentiation after ischemic stroke.
Authors: Marumo Et al.
Neurosci Res 2013;75:204
Generating regionalized neuronal cells from pluripotency, a step-by-step protocol.
Authors: Kirkeby Et al.
Front Cell Neurosci 2013;6:64
Common developmental pathways link tooth shape to regeneration.
Authors: Fraser Et al.
Dev Biol 2013;377:399
The role of Notch and γ-secretase inhibition in an ovarian cancer model.
Authors: Shah Et al.
J Neurosci 2013;33:801
Presenilin1 regulates histamine neuron development and behavior in zebrafish, danio rerio.
Authors: Sundvik Et al.
J Neurosci 2013;33:1589
Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia.
Authors: Díaz Et al.
J Cell Biol 2013;201:279
Inflammation-mediated notch signaling skews fanconi anemia hematopoietic stem cell differentiation.
Authors: Du Et al.
J Immunol 2013;191:2806
Shaping organs by a wingless-int/Notch/nonmuscle myosin module which orients feather bud elongation.
Authors: Li Et al.
Proc Natl Acad Sci U S A 2013;110:E1452
Opposing effects of bacitracin on human papillomavirus type 16 infection: enhancement of binding and entry and inhibition of endosomal penetration.
Authors: Campos Et al.
J Virol 2012;86:4169
Notch signaling inhibits axon regeneration.
Authors: Bejjani and Hammarlund
PLoS One 2012;73:268
Fibulin-3 promotes glioma growth and resistance through a novel paracrine regulation of Notch signaling.
Authors: Hu Et al.
Cancer Res 2012;72:3873
Jagged1 and Notch1 help edit M cell patterning in Peyer's patch follicle epithelium.
Authors: Hsieh and Lo
Dev Comp Immunol 2012;37:306
Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease.
Authors: Boulter Et al.
Nat Med 2012;18:572
Notch and TGFβ form a reciprocal positive regulatory loop that suppresses murine prostate basal stem/progenitor cell activity.
Authors: Valdez Et al.
RNA Biol 2012;11:676
Notch promotes vascular maturation by inducing integrin-mediated smooth muscle cell adhesion to the endothelial basement membrane.
Authors: Scheppke Et al.
Cell Stem Cell 2012;119:2149
Characterization of full-length and proteolytic cleavage fragments of desmoglein-2 in native human colon and colonic epithelial cell lines.
Authors: Kolegraff Et al.
Cell Adh Migr 2011;5:306
Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/β-catenin signaling.
Authors: Berndt Et al.
J Cell Biol 2011;194:737
Group II metabotropic glutamate receptor stimulation triggers production and release of Alzheimer's amyloid(β)42 from isolated intact nerve terminals.
Authors: Kim Et al.
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Reviews for DAPT
Average Rating: 4.8 (Based on 6 Reviews)
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For hPSC culture, final concentration 10 μM DAPT.
gamma -secretase (100 nM BMS 299897 and 250 nM DAPT)
Used successfully for the differentiation of iPSCs into dopaminergic neurons.
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.