| Chemical & Physical Properties | |
|---|---|
| CAS Number | 209984-56-5 |
| Catalog No. | 2A-1170289 |
| Chinese Name | γ-分泌酶抑制剂 |
| Synonyms | Deshydroxy LY-411575; DBZ; Dibenzazepine; YO-01027 |
| Molecular Formula | C26H23F2N3O3 |
| Molecular Weight | 463.476 |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 801.3±65.0 °C at 760 mmHg |
| Melting Point | 257-259ºC |
| Appearance | white to beige |
| Water Solubility | DMSO: soluble15mg/mL, clear |
| Storage Condition | -20°C Freezer |
| Application | YO-01027 (Dibenzazepine; DBZ) is a highly effective γ-secretase inhibitor with IC50s of 2.92±0.22 and 2.64±0.30 nM for cleaving Notch and APPL respectively. |
| HTC | 29337900 |
| PubChem ID | 16553096 |
| SMILES | CC(NC(=O)Cc1cc(F)cc(F)c1)C(=O)NC1C(=O)N(C)c2ccccc2-c2ccccc21 |
| InChI | 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 |
| InChI Key | QSHGISMANBKLQL-OWJWWREXSA-N |
| Hazard Symbols | transportation |
| Bioactivity | 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 Signaling Pathways >> Neuronal Signaling >> γ-secretase Signaling Pathways >> Stem Cell/Wnt >> γ-secretase Signaling Pathways >> Stem Cell/Wnt >> Notch Research Areas >> Cancer 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 [1]. Groth C, et al. Pharmacological analysis of Drosophila melanogaster gamma-secretase with respect to differential proteolysis of Notch and APP. Mol Pharmacol. 2010 Apr;77(4):567-74. [2]. Fuwa H, et al. Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic gamma-secretase inhibitors. ACS Chem Biol. 2007 Jun 15;2(6):408-18. [3]. Zheng YH, et al. Notch γ-secretase inhibitor dibenzazepine attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE knockout mice by multiple mechanisms. PLoS One. 2013 Dec 16;8(12):e83310. [4]. Xiao Z, et al. The Notch γ-secretase inhibitor ameliorates kidney fibrosis via inhibition of TGF-β/Smad2/3 signaling pathway activation. Int J Biochem Cell Biol. 2014 Oct;55:65-71. Chemical & Physical Properties 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 of Characters white to beige Vapour Pressure 0.0±2.8 mmHg at 25°C Index of Refraction 1.637 InChIKey QSHGISMANBKLQL-OWJWWREXSA-N SMILES CC(NC(=O)Cc1cc(F)cc(F)c1)C(=O)NC1C(=O)N(C)c2ccccc2-c2ccccc21 Storage condition -20°C Freezer Water Solubility DMSO: soluble15mg/mL, clear |
| Use of | Properties Name (2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide Synonym More Synonyms YO-01027 Biological Activity Related Catalog Signaling Pathways >> Neuronal Signaling >> γ-secretase Signaling Pathways >> Stem Cell/Wnt >> γ-secretase Signaling Pathways >> Stem Cell/Wnt >> Notch Research Areas >> Cancer 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]. References [1]. Groth C, et al. Pharmacological analysis of Drosophila melanogaster gamma-secretase with respect to differential proteolysis of Notch and APP. Mol Pharmacol. 2010 Apr;77(4):567-74. [2]. Fuwa H, et al. Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic gamma-secretase inhibitors. ACS Chem Biol. 2007 Jun 15;2(6):408-18. [3]. Zheng YH, et al. Notch γ-secretase inhibitor dibenzazepine attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE knockout mice by multiple mechanisms. PLoS One. 2013 Dec 16;8(12):e83310. Chemical & Physical Properties Molecular Formula C26H23F2N3O3 Exact Mass 463.170746 PSA 78.51000 Appearance of Characters white to beige Index of Refraction 1.637 InChIKey QSHGISMANBKLQL-OWJWWREXSA-N |
| Transport Info | Shipping Name: UN |
| MSDS Transport Info | Module 14. Shipping information 14.1 UN dangerous goods number European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.2 United Nations shipping name European Land Transport Dangerous Regulations: Non-dangerous goods IMDG Code: Non-dangerous goods International air transport dangerous goods regulations: non-dangerous goods 14.3 Transport hazard categories European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.4 Package group European Land Transport Dangerous Regulations: -International Maritime Dangerous Regulations: -International Air Transport Dangerous Regulations: - 14.5 Environmental hazards European Land Transport Danger Regulations: No International Maritime Danger Regulations International Air Transport Danger Regulations: No Marine pollutants (yes/no): No 14.6 Special reminder to users No data available |
| Related Products in Specialty Chemicals | ||
|---|---|---|
| 2,5-DICHLOROPHENETHYLAMINE | 56133-86-9 | 2A-1170284 |
| VX-702 | 479543-46-9 | 2A-1170284 |
| PF-01367338 | 459868-92-9 | 2A-1170285 |
| A-674563 | 552325-73-2 | 2A-1170287 |
| 5-(6-Quinoxalinylmethylene)-2,4-thiazolidinedione | 648450-29-7 | 2A-1170288 |
| PF-05212384 | 1197160-78-3 | 2A-1170290 |
| LY2886721 | 1262036-50-9 | 2A-1170291 |
| PF-04691502 | 1013101-36-4 | 2A-1170293 |
| PP242 | 1092351-67-1 | 2A-1170294 |
| KW-2478 | 819812-04-9 | 2A-1170295 |
| Browse all Specialty Chemicals products » | ||
Phone:
630-322-8886
630-322-8887
Email:
Office Locations:
Chicago, IL, USA
San Francisco, CA, USA
EN
SDS