209984-56-5
209984-56-5 structure
- Name: YO-01027
- Chemical Name: (2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide
- CAS Number: 209984-56-5
- Molecular Formula: C26H23F2N3O3
- Molecular Weight: 463.476
- Catalog: Biochemical Inhibitor Proteases Gamma-secretase inhibitor
- Create Date: 2018-08-11 17:14:54
- Modify Date: 2024-01-12 11:58:28
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YO-01027 (Dibenzazepine;DBZ) is a potent γ-secretase inhibitor with IC50 values of 2.92±0.22 and 2.64±0.30 nM for Notch and APPL cleavage, respectively.
| Name | (2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide |
|---|---|
| Synonyms |
N-[(3,5-Difluorophenyl)acetyl]-N-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide
Deshydroxy LY-411575 Benzeneacetamide, 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-difluoro- 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 DBZ Dibenzazepine YO-01027 |
| Description | YO-01027 (Dibenzazepine;DBZ) is a potent γ-secretase inhibitor with IC50 values of 2.92±0.22 and 2.64±0.30 nM for Notch and APPL cleavage, respectively. |
|---|---|
| Related Catalog | |
| Target |
IC50: 2.92±0.22 (Notch), 2.64±0.30 (APPL) nM[1] |
| In Vitro | Increasing concentrations of DBZ 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]. The molecular targets of CE and DBZ are the N-terminal fragment of presenilin 1 within the γ-secretase complex[2]. |
| In Vivo | DBZ blocks activated Notch1 signaling in abdominal aortic aneurysm (AAA) tissue from both Ang II-infused Apo E-/- mice and human undergoing AAA repair. DBZ markedly prevents Ang II-stimulated accumulation of macrophages and CD4+ T cells, and ERK-mediated angiogenesis, simultaneously reverses Th2 response, in vivo[3]. Administration of DBZ markedly attenuates renal fibrosis and expression of fibrotic markers, including collagen 1α1/3α1, fibronectin, and α-smoothmuscle actin. DBZ significantly inhibits ureteral obstruction -induced expression of transforming growth factor (TGF)- β, phosphorylated Smad 2, and Smad 3[4]. |
| Cell Assay | DBZ (0.1, 1, 2.5, 5, 7.5, 10, 25, 50, 100, 250 nM) are added to the S2 cell medium upon induction of Notch or APPL expression, 6 h before protein harvesting. For each sample, the same inhibitor is also included at the corresponding concentration in the lysis buffer for protein extraction and immunoblot analysis[1]. |
| Animal Admin | Mice: Male wild-type (WT) C57BL/6J and Apo E-/- mice are used in the study. Ang II-treated mice are received an intraperitoneal injection of either saline vehicle or γ-secretase inhibitor, dibenzazepine (DBZ) (1 mg/kg/d, dissolved in saline) 1 day before mini-pump implantation, and the treatment continued daily for 4 weeks. The blood pressure is measured in conscious mice using a computerized tail-cuff system. All mice are anesthetized. The aortic tissues are removed and prepared for further histological and molecular analysis[3]. |
| References |
| Density | 1.4±0.1 g/cm3 |
|---|---|
| Boiling Point | 801.3±65.0 °C at 760 mmHg |
| Melting Point | 257-259ºC |
| Molecular Formula | C26H23F2N3O3 |
| Molecular Weight | 463.476 |
| Flash Point | 438.4±34.3 °C |
| Exact Mass | 463.170746 |
| PSA | 78.51000 |
| LogP | 4.60 |
| Appearance | white to beige |
| Vapour Pressure | 0.0±2.8 mmHg at 25°C |
| Index of Refraction | 1.637 |
| Storage condition | -20°C Freezer |
| Water Solubility | DMSO: soluble15mg/mL, clear |