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Description: γ-secretase inhibitor; induces neuronal differentiation; blocks Notch signaling
Chemical Name: (2S)-N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine 1,1-dimethylethyl ester
Purity: ≥99% (HPLC)
Citations (53)
Reviews (6)
Protocols (3)
Literature (7)

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.

For more information about how DAPT may be used, see our protocols: Accelerated Induction of Cortical Neurons from hiPSCs, Human iPSC-derived Myoblasts, Generating Midbrain Dopaminergic Neurons from hPSCs.

DAPT synthesized to Ancillary Material Grade also available.

Scientific Data

Dopaminergic Neurons Derived from hiPSCs using DAPT. Dopaminergic neurons derived from human induced pluripotent stem cells (hiPSC) using SB 431542 (Catalog # 1614, Tocris), CHIR 99021 (Catalog # 4423, Tocris), DAPT and Purmorphamine (Catalog # 4551, Tocris). Cells cultured in Neuronal Media supplemented with TGF-3 (Catalog # 8420-B3, R&D Systems), cAMP, GDNF (Catalog # 212-GD, R&D Systems), BDNF (Catalog # 248-BDB, R&D Systems), N21-MAX (Catalog # AR008, R&D Systems). Differentiation shown at days 55 (left) and 62 (right). Images courtesy of Kevin Flynn, Bio-Techne.

Compound Libraries for DAPT

DAPT is also offered as part of the Tocriscreen 2.0 Max and Tocriscreen Stem Cell Library. Find out more about compound libraries available from Tocris.

Technical Data for DAPT

M. Wt 432.46
Formula C23H26F2N2O4
Storage Store at +4°C
Purity ≥99% (HPLC)
CAS Number 208255-80-5
PubChem ID 5311272
Smiles CC(C)(C)OC([C@H]([C@]2=CC=CC=C2)NC([C@H](C)NC(CC1=CC(F)=CC(F)=C1)=O)=O)=O

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
DMSO 43.24 100

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.

Select a batch to recalculate based on the batch molecular weight:
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

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*When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and CoA (available online).

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Product Datasheets for DAPT

Certificate of Analysis / Product Datasheet
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Keywords: DAPT, DAPT supplier, γ-secretase, gamma-secretase, inhibitors, inhibits, reduces, Aβ4, β42, beta42, levels, Proteinases, Proteases, β-Amyloid, beta-Amyloid, b-amyloid, Precursor, Protein, APP, beta, Peptides, amyloidbeta, amyloidb, amyloidβ, organoids, blocks, notch, signalin, Gamma-Secretase, Amyloid, Beta, Neural, Stem, Cells, Organoids, Retinal, 2634, Tocris Bioscience

53 Citations for DAPT

Citations are publications that use Tocris products. Selected citations for DAPT include:

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

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

Onai et al (2015) On the origin of vertebrate somites. Blood 1 33 PMID: 26613046

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

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

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

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

Sundvik et al (2013) Presenilin1 regulates histamine neuron development and behavior in zebrafish, danio rerio. J Neurosci 33 1589 PMID: 23345232

Kirkeby et al (2013) Generating regionalized neuronal cells from pluripotency, a step-by-step protocol. Front Cell Neurosci 6 64 PMID: 23316134

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

Fraser et al (2013) Common developmental pathways link tooth shape to regeneration. Dev Biol 377 399 PMID: 23422830

Xiang et al (2019) Long-term functional maintenance of primary human hepatocytes in vitro. Science 364 399 PMID: 31023926

Vila et al (2019) Quantification of human neuromuscular function through optogenetics. Theranostics 9 1232 PMID: 30867827

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

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

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

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

Bejjani and Hammarlund (2012) Notch signaling inhibits axon regeneration. PLoS One 73 268 PMID: 22284182

Pavlou et al (2014) Pleiotropic effects of Sox2 during the development of the zebrafish epithalamus. PLoS One 9 e87546 PMID: 24498133

Haidar et al (2019) Neuropathy-causing mutations in HSPB1 impair autophagy by disturbing the formation of SQSTM1/p62 bodies. Autophagy 15 1051 PMID: 30669930

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

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

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

Shah et al (2013) The role of Notch and γ-secretase inhibition in an ovarian cancer model. J Neurosci 33 801 PMID: 23482747

Guest et al (2016) Notch3 drives development and progression of cholangiocarcinoma Proc Natl Acad Sci U S A. 113 12250 PMID: 27791012

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

Gioia et al (2014) Mir-23a and mir-125b regulate neural stem/progenitor cell proliferation by targeting Musashi1. Anticancer Res 11 1105 PMID: 25483045

Alsanie (2017) Specification of murine ground state pluripotent stem cells to regional neuronal populations. Sci Rep 7 16001 PMID: 29167563

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

Schumacher (2017) ErbB4 signaling stimulates pro-inflammatory macrophage apoptosis and limits colonic inflammation. Cell Death Dis 8 e2622 PMID: 28230865

Tchieu et al (2017) A modular platform for differentiation of human PSCs into all major ectodermal lineages. Cell Stem Cell 21 399 PMID: 28886367

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

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

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

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

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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Filter by:

For hPSC culture.
By Anonymous on 06/30/2020
Assay Type: In Vitro
Species: Human
Cell Line/Tissue: Human PSC

For hPSC culture, final concentration 10 μM DAPT.

Make 100µl aliquots and keep them at −20 °C for up to 6 months.

review image

works well.
By Anonymous on 03/26/2020
Assay Type: In Vitro
Species: Rat
Cell Line/Tissue: Hippocampal neuron

gamma -secretase (100 nM BMS 299897 and 250 nM DAPT)

review image

The hiPSCs were maintained with Essential 8 Flex Medium with DAPT.
By Anonymous on 02/08/2020
Assay Type: In Vitro
Species: Human
Cell Line/Tissue: ipsc

2.5 μM

PMID: 29939162
review image

DAPT succesful for dopaminergic neuron differentiation.
By Anonymous on 01/23/2020
Assay Type: In Vitro
Species: Human

Used successfully for the differentiation of iPSCs into dopaminergic neurons.

Solubilised in DMSO.

review image

used in human cell line cultures.
By Anonymous on 08/20/2019
Assay Type: In Vitro
Species: Human

In cell line culture of human cells

Works great..
By Anonymous on 01/04/2018
Assay Type: In Vitro
Species: Human
Cell Line/Tissue: Induced pluripotent stem 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.

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