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Purity: =99.97%
YO-01027 (also called dibenzazepine; DBZ; YO01027) is a novel, potent, orally bioavailable, dipeptidic inhibitor of γ-secretase that may have antitumor effects. In cell-free assays for APPL and Notch cleavage, it inhibits γ-secretase with IC50s of 2.6 nM and 2.9 nM, respectively. High in vivo antitumor efficaciousness is demonstrated in C57BL/6 mice with MCF-7 tumors.
| Targets |
Notch (IC50 = 2.92±0.22 nM); APPL (IC50 = 2.64±0.30 nM)
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| ln Vitro |
YO-01027 targets the N-terminal Presenilin fragment and directly interacts with the γ-secretase complex. When APPL- or Notch-expressing cells are exposed to increasing concentrations of YO-01027, APPL CTF fragment accumulation progresses and NICD production declines in a strictly dose-dependent manner. (Source: ) YO-01027 at 10 μM decreases the quantity and activity of breast cancer stem cells (BCSCs).[2] According to a recent study, YO-01027 inhibits the production of the mucin protein MUC16 in undifferentiated cells via Notch inhibition at both the preconfluent and confluent stages, but not in postmitotic stratified cells. This effect is concentration-dependent.[3]
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| ln Vivo |
YO-01027 increases latency compared to control mice (18-28 days) and significantly reduces MCF7 tumors but not MDA-MB-231 tumors when administered intraperitoneally (1 mg/mL) on the day of cell injection and every 3 days after that. When MCF7 tumors did develop, they were considerably smaller thanks to YO-01027 treatment.[2] In intestine adenomas, YO-01027 treatment in C57BL/6 mice dose-dependently reduces the proliferation of epithelial cells and promotes goblet cell generation.[4]
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| Enzyme Assay |
To ascertain the effective linear range and maximal inhibitory dose of YO-01027, pilot studies are conducted utilizing varying drug concentrations spanning from 0.1 nM to 250 nM. When Notch or APPL expression is induced, six hours prior to protein harvesting, YO-01027 is added at the appropriate concentrations to the S2 cell medium. In the lysis buffer for protein extraction and immunoblot analysis, YO-01027 is additionally added for every sample at the appropriate concentration.
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| Cell Assay |
Resuspended cells at ≤1 × 106 are incubated with preconjugated primary antibodies BEREP4-FITC (1:10), CD44-APC (1:20), and CD24-PE (1:10) for 10 minutes at 4 °C in 100 μL sorting buffer (PBS containing 0.5% bovine serum albumin, 2 mM EDTA). After being cleaned with PBS, the cells are centrifuged for two minutes at 800 × g. Cells are resuspended in 500 μL of sorting buffer for analysis, and FACSCalibur is used to measure fluorescence and WinMIDI 2.8 is used for analysis. Following primary antibody incubation, cells are resuspended in 1× HBSS for sorting. Using FACSAria, cells are sorted at 16 p.s.i. with HBSS serving as the sheath fluid. The lowest quintile of CD24-positive cells plus all CD24-negative cells make up the CD24low cell population, which is gated by FACS.
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| Animal Protocol |
Mice: In this study, male C57BL/6J wild-type (WT) and Apo E-/- mice are used. Four weeks of daily treatment are administered to Ang II-treated mice via intraperitoneal injection, starting the day before mini-pump implantation and continuing every day thereafter with either a saline vehicle or the γ-secretase inhibitor dibenzazepine (DBZ) (1 mg/kg/d, dissolved in saline). Using an automated tail-cuff system, blood pressure is measured in conscious mice. Every rodent is sedated. To facilitate additional histological and molecular analysis, the aortic tissues are removed.
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| References |
| Molecular Formula |
C26H23F2N3O3
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|---|---|
| Molecular Weight |
463.48
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| Exact Mass |
463.17
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| Elemental Analysis |
C, 67.38; H, 5.00; F, 8.20; N, 9.07; O, 10.36
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| CAS # |
209984-56-5
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| Related CAS # |
YO-01027;209984-56-5
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| Appearance |
Yellow to orange solid powder.
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| SMILES |
C[C@@H](C(=O)N[C@H]1C2=CC=CC=C2C3=CC=CC=C3N(C1=O)C)NC(=O)CC4=CC(=CC(=C4)F)F
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| InChi Key |
QSHGISMANBKLQL-OWJWWREXSA-N
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| InChi Code |
InChI=1S/C26H23F2N3O3/c1-15(29-23(32)13-16-11-17(27)14-18(28)12-16)25(33)30-24-21-9-4-3-7-19(21)20-8-5-6-10-22(20)31(2)26(24)34/h3-12,14-15,24H,13H2,1-2H3,(H,29,32)(H,30,33)/t15-,24-/m0/s1
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| Chemical Name |
(2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide
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| Synonyms |
Dibenzazepine; YO01027; Iminostilbene; YO 01027; DBZ; YO-01027; Deshydroxy LY-411575
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.39 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 0.5% hydroxyethyl cellulose: 6 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1576 mL | 10.7880 mL | 21.5759 mL | |
| 5 mM | 0.4315 mL | 2.1576 mL | 4.3152 mL | |
| 10 mM | 0.2158 mL | 1.0788 mL | 2.1576 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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