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DAPT

Catalog #: 2634
53 Citations Datasheet
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2634/50
DAPT | CAS No. 208255-80-5 | Secretase Inhibitors
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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%

Product Details
Citations (53)
Reviews
Biological Activity Scientific Data Technical Data Background Product Datasheets Calculators

Biological Activity

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

N/A Using DAPT to differentiate hiPSCs into dopaminergic neurons View Larger

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.

Technical Data

M.Wt:
432.46
Formula:
C23H26F2N2O4
Solubility:
Soluble to 100 mM in DMSO
Purity:
≥99%
Storage:
Store at +4°C
CAS No:
208255-80-5

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.

Background References

  1. Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy.
    Schwab, Andrew J, Ebert, Allison
    PLoS ONE, 2014;9(7):e103112.
  2. Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4.
    Benner, Eric J, Luciano, Dominic, Jo, Rebecca, Abdi, Khadar, Paez-Gonzalez, Patricia, Sheng, Huaxin, Warner, David S, Liu, Chunlei, Eroglu, Cagla, Kuo, Chay T
    Nature, 2013;497(7449):369-73.
  3. Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors.
    Edri, Reuven, Yaffe, Yakey, Ziller, Michael, Mutukula, Naresh, Volkman, Rotem, David, Eyal, Jacob-Hirsch, Jasmine, Malcov, Hagar, Levy, Carmit, Rechavi, Gideon, Gat-Viks, Irit, Meissner, Alexande, Elkabetz, Yechiel
    Nat Commun, 2015;6(0):6500.
  4. Capturing the biology of disease severity in a PSC-based model of familial dysautonomia
    N Zeltner, F Fattahi, NC Dubois, N Saurat, F Lafaille, L Shang, B Zimmer, J Tchieu, MA Soliman, G Lee, JL Casanova, L Studer
    Nat. Med., 2016;22(12):1421-1427.
  5. Shaping organs by a wingless-int/Notch/nonmuscle myosin module which orients feather bud elongation.
    Li A, Chen M, Jiang T, Wu P, Nie Q, Widelitz R, Chuong C
    Proc Natl Acad Sci U S A, 2013;110(16):E1452-61.
  6. Mammary epithelial cell phagocytosis downstream of TGF-beta3 is characterized by adherens junction reorganization.
    Fornetti J, Flanders K, Henson P, Tan A, Borges V, Schedin P
    Cell Death Differ, 2016;23(2):185-96.
  7. Blocking p62/SQSTM1-dependent SMN degradation ameliorates Spinal Muscular Atrophy disease phenotypes
    N Rodriguez-, A Parkhitko, T Grass, RM Gibbs, EM Norabuena, N Perrimon, R Singh, LL Rubin
    J. Clin. Invest., 2018;0(0):.
  8. Opposing effects of bacitracin on human papillomavirus type 16 infection: enhancement of binding and entry and inhibition of endosomal penetration.
    Campos SK, Chapman JA, Deymier MJ, Bronnimann MP, Ozbun MA
    J. Virol., 2012;86(8):4169-81.
  9. Combinatorial analysis of developmental cues efficiently converts human pluripotent stem cells into multiple neuronal subtypes.
    Maury Y, Come J, Piskorowski R, Salah-Mohellibi N, Chevaleyre V, Peschanski M, Martinat C, Nedelec S
    Nat Biotechnol, 2015;33(1):89-96.
  10. Protective role of cellular prion protein against TNF?-mediated inflammation through TACE ?-secretase
    J Ezpeleta, F Boudet-Dev, M Pietri, A Baudry, V Baudouin, A Alleaume-B, N Dagoneau, O Kellermann, JM Launay, B Schneider
    Sci Rep, 2017;7(1):7671.
  11. Endocardial to myocardial notch-wnt-bmp axis regulates early heart valve development.
    Wang, Yidong, Wu, Bingruo, Chamberlain, Alyssa A, Lui, Wendy, Koirala, Pratisth, Susztak, Katalin, Klein, Diana, Taylor, Verdon, Zhou, Bin
    PLoS ONE, 2013;8(4):e60244.
  12. The COPII cargo adapter SEC24C is essential for neuronal homeostasis
    B Wang, JH Joo, R Mount, BJW Teubner, A Krenzer, AL Ward, VP Ichhaporia, EJ Adams, R Khoriaty, ST Peters, SM Pruett-Mil, SS Zakharenko, D Ginsburg, M Kundu
    J. Clin. Invest., 2018;0(0):.
  13. Hierarchical patterning modes orchestrate hair follicle morphogenesis
    JD Glover, KL Wells, F Matthäus, KJ Painter, W Ho, J Riddell, JA Johansson, MJ Ford, CAB Jahoda, V Klika, RL Mort, DJ Headon
    PLoS Biol., 2017;15(7):e2002117.
  14. Transcription factor PROX1 suppresses Notch pathway activation via the nucleosome remodeling and deacetylase complex in colorectal cancer stem-like cells
    J Högström, S Heino, P Kallio, M Lähde, VM Leppänen, D Balboa, Z Wiener, K Alitalo
    Cancer Res., 2018;0(0):.
  15. ErbB4 signaling stimulates pro-inflammatory macrophage apoptosis and limits colonic inflammation
    MA Schumacher, M Hedl, C Abraham, JK Bernard, PR Lozano, JJ Hsieh, D Almohazey, EB Bucar, S Punit, PJ Dempsey, MR Frey
    Cell Death Dis, 2017;8(2):e2622.
  16. A Snail1/Notch1 signalling axis controls embryonic vascular development.
    Wu Z, Rowe R, Lim K, Lin Y, Willis A, Tang Y, Li X, Nor J, Maillard I, Weiss S
    Nat Commun, 2014;5(0):3998.
  17. Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia.
    Diaz B, Yuen A, Iizuka S, Higashiyama S, Courtneidge S
    J Cell Biol, 2013;201(2):279-92.
  18. The notch response inhibitor DAPT enhances neuronal differentiation in embryonic stem cell-derived embryoid bodies independently of sonic hedgehog signaling.
    Crawford and Roelink
    Dev.Dyn., 2007;236:886
  19. Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.
    Dovey et al.
    J.Neurochem., 2001;76:173
  20. 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.
    Blood, 2005;106:3498
  21. SnapShot: Growing Organoids from Stem Cells.
    Sato et al.
    Cell, 2015;161:1700
  22. Central and Peripheral Nervous System Progenitors Derived from Human Pluripotent Stem Cells Reveal a Unique Temporal and Cell-Type Specific Expression of PMCAs
    M Chen, SH Laursen, M Habekost, CH Knudsen, SH Buchholdt, J Huang, F Xu, X Liu, L Bolund, Y Luo, P Nissen, F Febbraro, M Denham
    Front Cell Dev Biol, 2018;6(0):5.
  23. Chronic aerobic exercise improves insulin sensitivity and modulates Nrf2 and NF?kappaB/IkappaBalpha pathways in the skeletal muscle of rats fed with a high fat diet
    Q Yu, Z Xia, EC Liong, GL Tipoe
    Mol Med Rep, 2019;20(6):4963-4972.
  24. A Modular Differentiation System Maps Multiple Human Kidney Lineages from Pluripotent Stem Cells
    H Tsujimoto, T Kasahara, SI Sueta, T Araoka, S Sakamoto, C Okada, SI Mae, T Nakajima, N Okamoto, D Taura, M Nasu, T Shimizu, M Ryosaka, Z Li, M Sone, M Ikeya, A Watanabe, K Osafune
    Cell Rep, 2020;31(1):107476.
  25. Single-cell transcriptomics captures features of human midbrain development and dopamine neuron diversity in brain organoids
    A Fiorenzano, E Sozzi, M Birtele, J Kajtez, J Giacomoni, F Nilsson, A Bruzelius, Y Sharma, Y Zhang, B Mattsson, J Emnéus, DR Ottosson, P Storm, M Parmar
    Nature Communications, 2021;12(1):7302.
  26. MT5-MMP promotes neuroinflammation, neuronal excitability and Abeta production in primary neuron/astrocyte cultures from the 5xFAD mouse model of Alzheimer's disease
    D Pilat, JM Paumier, L García-Gon, L Louis, D Stephan, C Manrique, M Khrestchat, E Di Pasqual, K Baranger, S Rivera
    Journal of Neuroinflammation, 2022;19(1):65.
  27. Patient Derived Colonoids as Drug Testing Platforms-Critical Importance of Oxygen Concentration
    HK Skovdahl, S Gopalakris, TD Svendsen, AVB Granlund, I Bakke, ZG Ginbot, S Thorsvik, A Flatberg, B Sporsheim, J Ostrop, TE Mollnes, AK Sandvik, T Bruland
    Frontiers in Pharmacology, 2021;12(0):679741.
  28. Biphasic Activation of WNT Signaling Facilitates the Derivation of Midbrain Dopamine Neurons from hESCs for Translational Use
    TW Kim, J Piao, SY Koo, S Kriks, SY Chung, D Betel, ND Socci, SJ Choi, S Zabierowsk, BN Dubose, EJ Hill, EV Mosharov, S Irion, MJ Tomishima, V Tabar, L Studer
    Cell Stem Cell, 2021;28(2):343-355.e5.

Product Datasheets

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Citations for DAPT

The citations listed below are publications that use Tocris products. Selected citations for DAPT include:

53 Citations: Showing 1 - 10

  1. Biphasic activation of WNT signaling facilitates the derivation of midbrain dopamine neurons from hESCs for translational use.
    Authors: Kim Et al.
    Cell Stem Cell  2021;28:343
  2. Preclinical Efficacy and Safety of a Human Embryonic Stem Cell-Derived Midbrain Dopamine Progenitor Product, MSK-DA01
    Authors: Piao Et al.
    Cell Stem Cell  2021;28:217
  3. 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
  4. Quantification of human neuromuscular function through optogenetics.
    Authors: Vila Et al.
    Theranostics  2019;9:1232
  5. Long-term functional maintenance of primary human hepatocytes in vitro.
    Authors: Xiang Et al.
    Science  2019;364:399
  6. Neuropathy-causing mutations in HSPB1 impair autophagy by disturbing the formation of SQSTM1/p62 bodies.
    Authors: Haidar Et al.
    Autophagy  2019;15:1051
  7. 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
  8. 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
  9. A biodegradable hybrid inorganic nanoscaffold for advanced stem cell therapy.
    Authors: Yang
    Nat Commun  2018;9:3147
  10. Co-targeting of Tiam1/Rac1 and Notch ameliorates chemoresistance against dox. in a biomimetic 3D lymphoma model.
    Authors: Ikram Et al.
    Oncotarget  2018;9:2058
  11. 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
  12. Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector.
    Authors: Wang
    Nat Med  2018;24(5):647
  13. Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development.
    Authors: Gibb Et al.
    Development  2018;145
  14. The COPII cargo adapter SEC24C is essential for neuronal homeostasis.
    Authors: Wang Et al.
    J Clin Invest  2018;128:3319
  15. ErbB4 signaling stimulates pro-inflammatory macrophage apoptosis and limits colonic inflammation.
    Authors: Schumacher
    Cell Death Dis  2017;8:e2622
  16. 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.
    Oncotarget  2017;8:110426
  17. Specification of murine ground state pluripotent stem cells to regional neuronal populations.
    Authors: Alsanie
    Sci Rep  2017;7(1):16001
  18. 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
  19. Soluble Gamma-secretase Modulators Attenuate Alzheimer's β-amyloid Pathology and Induce Conformational Changes in Presenilin 1.
    Authors: Raven Et al.
    EBioMedicine  2017;24:93
  20. A modular platform for differentiation of human PSCs into all major ectodermal lineages.
    Authors: Tchieu Et al.
    Cell Stem Cell  2017;21:399
  21. 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
  22. Efficient Generation of Hypothalamic Neurons from Human Pluripotent Stem Cells.
    Authors: Wang Et al.
    Curr Protoc Hum Genet  2016;90:21.5.1
  23. Canonical Notch signaling plays an instructive role in auditory supporting cell development.
    Authors: Campbell Et al.
    Zoological Lett  2016;6:19484
  24. Generation of serotonin neurons from human pluripotent stem cells.
    Authors: Lu Et al.
    Nat Biotechnol  2016;34:89
  25. Capturing the biology of disease severity in a PSC-based model of familial dysautonomia.
    Authors: Zeltner Et al.
    Nat Med  2016;22:1421
  26. Notch3 drives development and progression of cholangiocarcinoma
    Authors: Guest Et al.
    Proc Natl Acad Sci U S A.  2016;113:12250
  27. Analysing human neural stem cell ontogeny by consecutive isolation of Notch active neural progenitors.
    Authors: Edri Et al.
    Nat Commun  2015;6:6500
  28. Generation of clinical-grade human induced pluripotent stem cells in Xeno-free conditions.
    Authors: Wang Et al.
    Stem Cell Res Ther  2015;6:223
  29. On the origin of vertebrate somites.
    Authors: Onai Et al.
    Blood  2015;1:33
  30. A small molecule targeting ALK1 prevents Notch cooperativity and inhibits functional angiogenesis.
    Authors: Kerr Et al.
    Angiogenesis  2015;18:209
  31. 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
  32. Pleiotropic effects of Sox2 during the development of the zebrafish epithalamus.
    Authors: Pavlou Et al.
    PLoS One  2014;9:e87546
  33. Astrocyte-derived endothelin-1 inhibits remyelination through notch activation.
    Authors: Hammond Et al.
    Neuron  2014;81:588
  34. Canonical Notch signalling is inactive in urothelial carcinoma.
    Authors: Greife Et al.
    BMC Cancer  2014;14:628
  35. Mir-23a and mir-125b regulate neural stem/progenitor cell proliferation by targeting Musashi1.
    Authors: Gioia Et al.
    Anticancer Res  2014;11:1105
  36. Notch signaling regulates nucleocytoplasmic Olig2 translocation in reactive astrocytes differentiation after ischemic stroke.
    Authors: Marumo Et al.
    Neurosci Res  2013;75:204
  37. Generating regionalized neuronal cells from pluripotency, a step-by-step protocol.
    Authors: Kirkeby Et al.
    Front Cell Neurosci  2013;6:64
  38. Common developmental pathways link tooth shape to regeneration.
    Authors: Fraser Et al.
    Dev Biol  2013;377:399
  39. The role of Notch and γ-secretase inhibition in an ovarian cancer model.
    Authors: Shah Et al.
    J Neurosci  2013;33:801
  40. Presenilin1 regulates histamine neuron development and behavior in zebrafish, danio rerio.
    Authors: Sundvik Et al.
    J Neurosci  2013;33:1589
  41. 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
  42. Inflammation-mediated notch signaling skews fanconi anemia hematopoietic stem cell differentiation.
    Authors: Du Et al.
    J Immunol  2013;191:2806
  43. 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
  44. 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
  45. Notch signaling inhibits axon regeneration.
    Authors: Bejjani and Hammarlund
    PLoS One  2012;73:268
  46. Fibulin-3 promotes glioma growth and resistance through a novel paracrine regulation of Notch signaling.
    Authors: Hu Et al.
    Cancer Res  2012;72:3873
  47. Jagged1 and Notch1 help edit M cell patterning in Peyer's patch follicle epithelium.
    Authors: Hsieh and Lo
    Dev Comp Immunol  2012;37:306
  48. 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
  49. 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
  50. 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
  51. 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
  52. 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
  53. 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.
    Neuron  2010;30:3870

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