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Description: γ-secretase inhibitor; inhibits Notch pathway
Alternative Names: Dibenzazepine,YO-01027
Chemical Name: N-[(1S)-2-[[(7S)-6,7-Dihydro-5-methyl-6-oxo-5H-dibenz[b,d]azepin-7-yl]amino]-1-methyl-2-oxoethyl]-3,5-difluorobenzeneacetamide
Purity: ≥98% (HPLC)
Biological Activity for DBZ
DBZ is an inhibitor of γ-secretase aspartyl protease. DBZ blocks amyloid precursor protein-like (APPL) and Notch cleavage (IC50 values are 2.6 nM and 1.7-2.9 nM, respectively). By inhibiting Notch and the Notch pathway, DBZ improves efficiency of iPSC generation and production of iPSCs from mouse and human keratinocytes without KLF4 and CMYC. In an animal model of Alzheimer's disease, DBZ inhibits the cleavage of amyloid precursor protein into Aβ40. DBZ promotes cochlear supporting cell proliferation and hair cell mitotic regeneration in neonatal mice. DBZ in combination with iDOT1L enables maintenance of human naïve-state pluripotency in non-hypoxic conditions.
DBZ synthesized to Ancillary Material Grade also available.
Compound Libraries for DBZ
DBZ 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 DBZ
| M. Wt | 463.48 |
| Formula | C26H23F2N3O3 |
| Storage | Store at -20°C |
| Purity | ≥98% (HPLC) |
| CAS Number | 209984-56-5 |
| PubChem ID | 11454028 |
| InChI Key | QSHGISMANBKLQL-OWJWWREXSA-N |
| Smiles | CN1C2=C(C=CC=C2)C3=C(C=CC=C3)[C@H](NC([C@@H](NC(CC4=CC(F)=CC(F)=C4)=O)C)=O)C1=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 DBZ
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 46.35 | 100 |
Preparing Stock Solutions for DBZ
The following data is based on the product molecular weight 463.48. 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 | 2.16 mL | 10.79 mL | 21.58 mL |
| 5 mM | 0.43 mL | 2.16 mL | 4.32 mL |
| 10 mM | 0.22 mL | 1.08 mL | 2.16 mL |
| 50 mM | 0.04 mL | 0.22 mL | 0.43 mL |
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Product Datasheets for DBZ
References for DBZ
References are publications that support the biological activity of the product.
Groth et al (2010) Pharmacological analysis of Drosophila melanogaster γ-secretase with respect to differential proteolysis of Notch and APP. Mol.Pharmacol. 77 567 PMID: 20064975
van Es et al (2005) Notch/γ-secretase inhibition turns proliferative cells in intestinal crypts and adenomas into goblet cells. Nature 435 959 PMID: 15959515
Ichida et al (2014) Notch inhibition allows oncogene-independent generation of iPS cells. Nat.Chem.Biol. 10 632 PMID: 24952596
Wu et al (2020) Dibenzazepine promotes cochlear supporting cell proliferation and hair cell regeneration in neonatal mice. Cell Prolif. 53 e12872 PMID: 32677724
Isono et al (2020) The combination of dibenzazepine and a DOT1L inhibitor enables a stable maintenance of human naïve-state pluripotency in non-hypoxic conditions. Regen.Ther. 15 161 PMID: 33426214
If you know of a relevant reference for DBZ, please let us know.
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Keywords: DBZ, DBZ supplier, Notch, inhibitors, inhibits, gamma, γ, g-secretases, signaling, signalling, pathways, gamma-secretase, amyloid, stem, cells, iPSCs, induced, pluripotent, reprogramming, dedifferentiation, YO01027, YO-01027, alzheimers, APP, Ab, Abeta, Dibenzazepine, Gamma-Secretase, Stem, Cell, Reprogramming, Organoids, 4489, Tocris Bioscience
21 Citations for DBZ
Citations are publications that use Tocris products. Selected citations for DBZ include:
Khan et al (2018) The deubiquitinase USP9X regulates FBW7 stability and suppresses colorectal cancer. J Clin Invest 128 1326 PMID: 29346117
Chen et al (2018) Cancer-associated fibroblasts suppress SOX2-induced dysplasia in a lung squamous cancer coculture. Proc Natl Acad Sci U S A 115 E11671 PMID: 30487219
Varda et al (2021) Principles of signaling pathway modulation for enhancing human naive pluripotency induction. Cell Stem Cell 28 1549-1565.e12 PMID: 33915080
Ling et al (2021) Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids. Cell Stem Cell 28 1090-1104.e6 PMID: 33915081
Cong et al (2021) Soluble guanylate cyclase signalling mediates etoposide resistance in progressing small cell lung cancer. Nat Commun 12 6652 PMID: 34789728
Cecilia et al (2021) Mapping the temporal and spatial dynamics of the human endometrium in vivo and in vitro. Nat Genet 53 1698-1711 PMID: 34857954
Karen E et al (2021) Direct SARS-CoV-2 infection of the human inner ear may underlie COVID-19-associated audiovestibular dysfunction. Commun Med (Lond) 1 44 PMID: 34870285
Bi et al (2014) Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity. Nat Med 20 911 PMID: 25038826
Page et al (2019) Positive Feedback Defines the Timing, Magnitude, and Robustness of Angiogenesis. Cell Rep 27 3139 PMID: 31189101
Kari et al (2018) Transcription Factor PROX1 Suppresses Notch Pathway Activation via the Nucleosome Remodeling and Deacetylase Complex in Colorectal Cancer Stem-like Cells. Cancer Res 78 5820-5832 PMID: 30154153
Bi et al (2016) Stage-specific effects of Notch activation during skeletal myogenesis. Elife 5 PMID: 27644105
Shah et al (2013) The role of Notch and γ-secretase inhibition in an ovarian cancer model. J Reprod Dev 33 801 PMID: 23482747
Yung et al (2019) Sufu- And Spop-mediated downregulation of Hedgehog signaling promotes beta cell differentiation through organ-specific niche signals. Nat.Commun. 10 4647 PMID: 31604927
Santos et al (2019) Urothelial organoids originating from Cd49fhigh mouse stem cells display Notch-dependent differentiation capacity. Nat.Commun. 10 4407 PMID: 31562298
Marshall et al (2018) Analysis of the Intrinsic Self-Organising Properties of Mesenchymal Stromal Cells in Three-Dimensional Co-Culture Models with Endothelial Cells. Bioengineering (Basel) 5 PMID: 30373192
Timothy C et al (2022) Contribution of Trp63CreERT2-labeled cells to alveolar regeneration is independent of tuft cells. Elife 11 PMID: 36129169
S A et al (2019) Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature 575 512-518 PMID: 31597160
Bi et al (2016) Notch activation drives adipocyte dedifferentiation and tumorigenic transformation in mice. J Exp Med 213 2019 PMID: 27573812
Harshil et al (2020) The Transcription Co-Repressors MTG8 and MTG16 Regulate Exit of Intestinal Stem Cells From Their Niche and Differentiation Into Enterocyte vs Secretory Lineages. Gastroenterology 159 1328-1341.e3 PMID: 32553763
Fan et al (2020) A Notch3-Marked Subpopulation of Vascular Smooth Muscle Cells Is the Cell of Origin for Occlusive Pulmonary Vascular Lesions. Circulation 142 1545-1561 PMID: 32794408
Ihara et al (2016) TGF-β Signaling in Dendritic Cells Governs Colonic Homeostasis by Controlling Epithelial Differentiation and the Luminal Microbiota. J Immunol 196 4603 PMID: 27183608
Do you know of a great paper that uses DBZ from Tocris? Please let us know.
Reviews for DBZ
Average Rating: 3 (Based on 1 Review.)
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DBZ.
By
Minjin Jeong on 09/09/2019
Assay Type: In Vivo
Species: Mouse
Cell Line/Tissue: iPSCs
Differentiation of hiPSCs into optic progenitor cells.
For obtaining a higher solubility, I recommend warming at 37°C.
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Stem Cell Research Product Guide
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