For research use only. Not for therapeutic Use.
YO-01027 (Dibenzazepine;DBZ) is a potent γ-secretase inhibitor with IC50 values of 2.92 and 2.64 nM for Notch and APPL cleavage, respectively.
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].
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].
| Catalog Number | R009585 |
| CAS Number | 209984-56-5 |
| Synonyms | (2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide |
| Molecular Formula | C26H23F2N3O3 |
| Purity | ≥95% |
| 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 |
| InChIKey | QSHGISMANBKLQL-OWJWWREXSA-N |
| SMILES | CC(C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3N(C1=O)C)NC(=O)CC4=CC(=CC(=C4)F)F |
| Reference | [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. |
