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Dibenzazepine (YO-01027)

Name: Dibenzazepine (YO-01027)
Brand: Selleck Chemicals
SKU: S2711
Rating: 5 (28 reviews)

Catalog No.S2711 Synonyms: DBZ

For research use only.

Dibenzazepine (YO-01027, DBZ) is a dipeptidic γ-secretase inhibitor with IC50 of 2.6 nM and 2.9 nM in cell-free assays for APPL and Notch cleavage, respectively.

Dibenzazepine (YO-01027) Chemical Structure

CAS No. 209984-56-5

Selleck's Dibenzazepine (YO-01027) has been cited by 28 publications

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Gamma-secretase Signaling Pathway Map

Biological Activity

Description

Dibenzazepine (YO-01027, DBZ) is a dipeptidic γ-secretase inhibitor with IC50 of 2.6 nM and 2.9 nM in cell-free assays for APPL and Notch cleavage, respectively.

Targets

γ secretase(APPL) ^[1] (Cell-free assay)	Notch ^[1] (Cell-free assay)
2.6 nM	2.9 nM

In vitro

YO-01027 interacts directly with theγ-secretase complex and targets the N-terminal Presenilin fragment. Increasing concentrations of YO-01027 administered to APPL- or Notch-expressing cells leads to the progressive accumulation of APPL CTF fragments and a decrease in NICD production in a strictly dose-dependent manner. ^[1] 10 μM of YO-01027 reduces breast cancer stem cells (BCSC) number and activity. ^[2] A recent research indicates YO-01027 impairs mucin protein MUC16 biosynthesis in a concentration-dependent manner in undifferentiated cells at both preconfluent and confluent stages through Notch inhibition, but not in postmitotic stratified cells. ^[3]

Cell Data

Cell Lines	Assay Type	Concentration	Incubation Time	Formulation	Activity Description	PMID

SupT1	Ml36SpVv[3Srb36gZZN{[Xl?	M{joXlE3KGi{cx?=	NVGzR4VlUW6qaXLpeIlwdiCxZjDnZY1u[SC\|ZXPy[ZRie2ViaX6gbJVu[W5iU4XwWFEh[2WubIOgZZN{\XO\|ZXSgZZMhemWmdXP0bY9vKGmwIHHtfYxwcWRiYnX0ZUA1OCCjZoTldkAyPiCqcoOgZpkh[2inbXnseY1qdmW\|Y3XuZ4Uh[XO\|YYmsJGlEPTB;MD6wNFI3\|ryP	NF22ZXc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{N{C0OVk4PSd-MkewOFU6PzV:L3G+
SupT1	MXvGeY5kfGmxbjDhd5NigQ>?	MV[xOkBpenN?	M2LXTWlvcGmkaYTpc44hd2ZiZ3HtcYEhe2WlcnX0ZZNmKG2nZHnheIVlKE6xdHPoJJNq\26jbHnu[{BqdiCqdX3hckBUfXCWMTDj[YxteyCjZoTldkAyPiCqcoOgZpkh[2inbXnseY1qdmW\|Y3XuZ4Uh[XO\|YYmsJGlEPTB;MD6wNFI6\|ryP	MlT0QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjdyNEW5O\|UoRjJ5MES1PVc2RC:jPh?=
DAOY	NVW0T\|hDeUiWUzDhd5NigQ>?		M{fkfJFJXFNib3[gdIVlcWG2cnnjJINidmOncjDj[YxtKGyrbnXzJJRwKGmmZX70bYZ6KG23bITpdIxmKG:ycH;yeJVvcXSrZYOg[o9zKGS{dXegdoVxfXKyb4Ppcoc7KFC{aX3hdpkhe2O{ZXXuJIZweiCGQV;ZJINmdGy\|	NH7xTm89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
A673	MVPxTHRUKGG\|c3H5		MVLxTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhSTZ5MzDj[Yxtew>?	NIDKXpc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{OUSzOVE{QSd-Mkm0N\|UyOzl:L3G+
SK-N-MC	MYXxTHRUKGG\|c3H5		MV7xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhW0tvTj3NR{Bk\Wyucx?=	M325VlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
SK-N-SH	MVHxTHRUKGG\|c3H5		NW\hc4lFeUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGPLMW4uW0hiY3XscJM>	MnjCQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjl2M{WxN\|koRjJ7NEO1NVM6RC:jPh?=
NB1643	MnPtdWhVWyCjc4PhfS=>		MU\xTHRUKG:oIIDl[IlifHKrYzDjZY5k\XJiY3XscEBtcW6nczD0c{Bq\GWwdHnmfUBufWy2aYDs[UBweHCxcoT1col1cWW\|IH\vdkBlenWpIILldJVzeG:\|aX7nPkBRemmvYYL5JJNkemWnbjDmc5IhVkJzNkSzJINmdGy\|	M1fWTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ7NEO1NVM6Lz5{OUSzOVE{QTxxYU6=
RD	NF7VfZJyUFSVIHHzd4F6		NULVN5pneUiWUzDv[kBx\WSrYYTybYMh[2GwY3XyJINmdGxibHnu[ZMhfG9iaXTlcpRq\nlibYXseIlxdGVib4Dwc5J1fW6rdHnld{Bnd3JiZIL1[{Bz\XC3coDvd4lv\zpiUILpcYFzgSC\|Y4Ll[Y4h\m:{IGLEJINmdGy\|	NVToWoUzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
MG 63 (6-TG R)	MkHrdWhVWyCjc4PhfS=>		MlnVdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKE2JIE[zJEg3NVSJIGKpJINmdGy\|	NYTsO2Y5RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>
Rh41	NFP3VXdyUFSVIHHzd4F6		MknOdWhVWyCxZjDw[YRq[XS{aXOgZ4Fv[2W{IHPlcIwhdGmwZYOgeI8hcWSnboTp[pkhdXWudHnwcIUhd3Cyb4L0eY5qfGmnczDmc5Ih\HK3ZzDy[ZB2enCxc3nu[\|ohWHKrbXHyfUB{[3KnZX6g[o9zKFKqNEGgZ4VtdHN?	NUHsZmhMRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC\|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkm0N\|UyOzlpPkK5OFM2OTN7PD;hQi=>

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In vivo

YO-01027, which is delivered 1 mg/mL by i.p. injection on the day of cell injection and every subsequent 3 days, YO-01027 significantly, decreases MCF7 but not MDA-MB-231 tumors and increases latency compared with control mice (18-28 days). YO-01027-treated MCF7 tumors that did form had significantly reduced tumor volumes. ^[2] Treatment of YO-01027 into C57BL/6 mice inhibits epithelial cell proliferation and induces goblet cell differentiation in intestinal adenomas in a dose-dependent manner. ^[4]

Protocol (from reference)

Kinase Assay: ^[1]	Pharmacological Inhibition of γ-secretase Activity: For YO-01027, pilot experiments are performed with different drug concentrations ranging from 0.1 nM to 250 nM to determine the effective linear range and maximal inhibition dose for YO-01027. YO-01027 is added at the required concentrations to the S2 cell medium upon induction of Notch or APPL expression, 6 hours before protein harvesting. For each sample, YO-01027 is also included at the corresponding concentration in the lysis buffer for protein extraction and immunoblot analysis.
Cell Research: ^[2]	Cell lines: BCSC Concentrations: 10 μM Incubation Time: 3 days Method: Cells are resuspended at ≤1 × 10⁶ in 100 μL sorting buffer (PBS containing 0.5% bovine serum albumin, 2 mM EDTA) and incubated with preconjugated primary antibodies BEREP4-FITC (1:10), CD44-APC (1:20), and CD24-PE (1:10) for 10 minutes at 4 °C. The cells are washed in PBS and centrifuged at 800 × g for 2 minutes. For analysis, cells are resuspended in 500 μL of sorting buffer and fluorescence is measured using FACSCalibur and analyzed using WinMIDI 2.8. For sorting, cells are resuspended in 1× HBSS after incubation with the primary antibodies. Cells are sorted, with HBSS as sheath fluid, at 16 p.s.i. using FACSAria. The CD24_low cell population gated by FACS is the lowest quintile of CD24-positive cells plus all the CD24-negative cells.
Animal Research: ^[4]	Animal Models: C57BL/6 mice Dosages: 0, 3, 10, 30 μmol/kg Administration: Injected daily intraperitoneally

References

[4] Van Es JH, et al, Nature, 2005, 435(7044), 959-963.

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Solubility (25°C)

In vitro	DMSO	92 mg/mL (198.49 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order (Data is from Selleck tests instead of citations): 0.5% hydroxyethyl cellulose For best results, use promptly after mixing.	6 mg/mL

Chemical Information

Molecular Weight	463.48
Formula	C₂₆H₂₃F₂N₃O₃
CAS No.	209984-56-5
Storage	3 years	-20°C	powder
Storage	2 years	-80°C	in solvent
Smiles	CC(C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3N(C1=O)C)NC(=O)CC4=CC(=CC(=C4)F)F

Download Dibenzazepine (YO-01027) SDF

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Question 1:
How to dissolve the compund for in vivo applications?

Answer:
For S2711, we suggest to use 0.5% hydroxyethyl cellulose in vivo study.

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