Dibenzazepine (YO-01027) 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.
NSG mice were engrafted with human DND41 cells in 3 independent experiments. After DBZ treatment, marrow leukemia burden was determined by the expression of human CD45 (hCD45). Host LSK (hCD45−) (A), OB (B) and MSC frequencies (C) were determined by FACS in control (receiving culture medium) or in xenografted mice treated with vehicle or DBZ (n=8–9.group).
Cancer Res, 2016, 76(6):1641-52. Dibenzazepine (YO-01027) purchased from Selleck.
Inhibition of Notch signaling by dibenzazepine (DBZ) leads to decreased cell proliferation and secretory cell hyperplasia. The intestine isolated from stage‐56/57 tadpoles was cultured with 20 nM T3 for 5 (A-F) or 7 (G-J) days in the presence of DMSO (A, C, E, G, I) or 10 μM DBZ (B, D, F, H, J) after precultivation of the isolated intestinal fragments with DMSO or 10 μM DBZ for 3 days (see Fig. Fig.4A).4A). Cryosections of the intestinal fragments were hybridized with antisense Hairy1 (A, B) or Hairy2b (C, D). Paraffin sections were incubated with anti‐PCNA (E, F) or anti-IFABP (G, H) antibodies or subjected to Periodic acid‐Schiff (PAS) staining followed by counter-staining with hematoxylin (I, J). As a control, paraffin sections of the intestine from wild type froglets at stage 66 were also stained with PAS to identify goblet cells (K, arrowheads). Note that after 5 days, TH‐induced up‐regulation of Hairy genes (A, C, arrowheads) was impaired by DBZ treatment in vitro (B, D). PCNA‐positive epithelial cells also decreased by DBZ treatment (E, F, arrowheads). After 7 days, IFABP was detected in most of the newly formed adult epithelial cells of the control intestine (G, arrowheads), but not the DBZ-treated intestine (H). A small number of goblet cell was detected in the control intestine (I, arrowhead), whereas PAS-positive secretory cells increased by DBZ treatment (J, arrowheads). The dashed-lines indicate the boundary of the epithelium and the connective tissue. Scale bars = 20 μm. Abbreviations: CT, connective tissue, DBZ, dibenzazepine, Ep, epithelium, PAS, Periodic acid‐Schiff.
Stem Cells, 2017, 35(4):1028-1039. Dibenzazepine (YO-01027) purchased from Selleck.
Overexpression of PrP enhances Notch1 signaling and cancer cell growth and invasion. Capan-1 cells were transfected with control or PrP-expressing plasmid. A: Expression of PrP, Notch1, and Hes1 was assessed by immunoblotting. N1 and Hes1 expression was also assessed after DBZ treatment (20 μmol/L for 48 hours) (right two columns). B and C: PrP-OE increases cell growth (B) and migration (C), although DBZ treatment decelerates Capan-1 proliferation and migration. D: Control or PrP-OE Capan-1 cells were injected ipsilaterally on the back of nude mice. Paired animals received either PBS (control or PrP-OE) or DBZ (control + DBZ or PrP-OE + DBZ) for 3 consecutive days every 7 days. Tumors were dissected at the end of 6 weeks. Tumor volumes were measured weekly and at the end of experiments. Data are expressed as means ± SD. t-test was performed (B–D). n = 3 independent experiments (A); n = 6 mice (B and C); n = 8 biological replicates (B and C); n = 5 mice in each group (D). ∗P < 0.05, ∗∗P < 0.01. Ctrl, control; DBZ, dibenzazepine; N1, Notch1; OE, overexpression; PBS, phosphate-buffered saline; PrP, prion protein.
Am J Pathol, 2016, 186(11):2945-2956. Dibenzazepine (YO-01027) purchased from Selleck.
|製品説明||Dibenzazepine (YO-01027) 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.|
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.  10 μM of YO-01027 reduces breast cancer stem cells (BCSC) number and activity.  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. 
|体内試験||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.  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. |
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.
|体外||DMSO||92 mg/mL (198.49 mM)|
0.5% hydroxyethyl cellulose
質量 (g) = 濃度 (mol/L) x 体積 (L) x 分子量 (g/mol)
開始濃度 x 開始体積 = 最終濃度 x 最終体積
この方程式は、一般に略語を使われます：C1V1 = C2V2 ( 入力 出力 )
チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2
How to dissolve the compund for in vivo applications?
For S2711, we suggest to use 0.5% hydroxyethyl cellulose in vivo study.