565790

Compound E

≥95% (HPLC), solid, γ-secretase inhibitor, Calbiochem^®

• Sinonimo/i: γ-Secretase Inhibitor XXI, Compound E, (S,S)- 2-[2-(3,5-Difluorophenyl)-acetylamino]-N-(1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-propionamide, Compound E
• Formula empirica (notazione di Hill): C₂₇H₂₄F₂N₄O₃
• Numero CAS: 209986-17-4
• Peso molecolare: 490.50
• MDL number: MFCD04974531
• UNSPSC Code: 12352200
• NACRES: NA.77
• Assay: ≥95% (HPLC)
• Form: solid
• Quality level: 300
• Storage condition: OK to freeze, protect from light

Proprietà

• Nome del prodotto: γ-Secretase Inhibitor XXI, Compound E, This g-secretase inhibitor, CAS 209986-17-4, is a cell-permeable, potent, selective, non-transition-state analog inhibitor of γ-secretase and Notch processing. Lowers Aβ levels in APP transgenic mice
• Quality Level: 300
• assay: ≥95% (HPLC)
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze, protect from light
• color: white
• solubility: DMSO: 10 mg/mL
• shipped in: ambient
• storage temp.: 2-8°C
• SMILES string: Fc1cc(cc(c1)CC(=O)N[C@@H](C)C(=O)NC2N=C(c4c(cccc4)N(C2=O)C)c3ccccc3)F
• InChI: 1S/C27H24F2N4O3/c1-16(30-23(34)14-17-12-19(28)15-20(29)13-17)26(35)32-25-27(36)33(2)22-11-7-6-10-21(22)24(31-25)18-8-4-3-5-9-18/h3-13,15-16,25H,14H2,1-2H3,(H,30,34)(H,32,35)/t16-,25?/m0/s1
• InChI key: JNGZXGGOCLZBFB-YPHZTSLFSA-N

Descrizione

General description

A cell-permeable, potent, selective, peptidomimetic, non-transition-state analog inhibitor of γ-secretase and Notch processing (IC₅₀ = 300 pM for Aβ₄₀ in CHO cells overexpressing wild type βAPP; 240 pM for Aβ₄₀, 370 pM for Aβ₄₂, and 320 pM for NICD, respectively, in HEK293 cells stably transfected with βAPP₆₉₅ and mNotchΔE(M1727V); 100 pM for both Aβ₄₀ and Aβ₄₂ in SH-SY5Y cells stably transfected with SPA4CT). Lowers Aβ levels in several APP transgenic mouse models. Reported to bind to presenilins and suppress the proteolytic cleavage of transmembrane protein substrates, including APLP1 and APLP2, CD44, ErbB4, E-cadherin, low density lipoprotein receptor-related proteins, Notch ligands, and p75^NTR. Only weakly affects presenilinase activity at much higher concentrations (200-400 µM).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
γ-secretase and Notch processing Ab40 in CHO cells overexpressing wild type bAPP

Product does not compete with ATP.

Reversible: no

Target IC₅₀: 300 pM for Aβ40 in CHO cells overexpressing wild typeβAPP; 240 pM for Aβ40, 370 pM for Aβ42, and 320 pM for NICD, respectively, in HEK293 cells stably transfected with βAPP695 and mNotchΔE(M1727V); 100 pM for both Aβ40

Packaging

Packaged under inert gas

Preparation Note

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Other Notes

Milano, J., et al. 2004. Toxicol. Sci.82, 341.
Jung, K.M., et al. 2003. J. Biol. Chem.278, 42161.
Murakami, D., et al. 2003. Oncogene22, 1511.
Campbell, W.A., et al. 2003. J. Neurochem.85, 1563.
Berechid, B.E., et al., 2002. J. Biol. Chem.277, 8154.
Lee, H.J., et al. 2002. J. Biol. Chem.277, 6318.
May, P., et al. 2002. J. Biol. Chem.277, 18736.
Scheinfeld, M.H., et al. 2002. J. Biol. Chem.277, 44195.
Ni, C. Y., et al. 2001. Science294, 2179.
Beher, D., et al. 2001. J. Biol. Chem.276, 45394.
Doerfler, P., et al. 2001. Proc. Natl. Acad. Sci. USA98, 9312.
Seiffert, D., et al. 2000. J. Biol. Chem.275, 34086.

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Disclaimer

Toxicity: Standard Handling (A)

Informazioni sulla sicurezza

• Classe di stoccaggio: 11 - Combustible Solids
• wgk: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable