L-685,458

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L-685,458

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

CAS NO:	292632-98-5
规格:	≥98%

包装与价格：

包装	价格(元)
2mg	电议
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议

产品介绍

L-685,458 (also called L685458; L-685458) is a selective inhibitor of Ass PP γ-secretase with potential anti-AD and anticancer activity. It inhibits Ass PP γ-secretase with a Ki of 17 nM and shows more than 50-fold selectivity over a range of aspartyl, serine and cysteine proteases. L685458 is also equally potent in the inhibition of A β 40 and A β 42 peptides with IC50 values of 48 and 67 nM, respectively in human neuroblastoma cells. It regulates CXCR4 and VEGFR2 expression through blocking of Notch signaling in vitro as observed in the two cell lines in terms of reduced cytoplasmic distribution and almost diminished nuclear labelling of Hes1 proteins

理化性质和储存条件

Molecular Weight (MW)	672.85
Formula	C39H52N4O6
CAS No.	292632-98-5
Storage	-20℃ for 3 years in powder form
Storage	-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 100 mg/mL (148.6 mM)
	Water: <1 mg/mL
	Ethanol: 6 mg/mL warmed (8.9 mM)
Other info	Chemical Name: tert-butyl ((2S,3R,5R)-6-(((S)-1-(((S)-1-amino-1-oxo-3-phenylpropan-2-yl)amino)-4-methyl-1-oxopentan-2-yl)amino)-5-benzyl-3-hydroxy-6-oxo-1-phenylhexan-2-yl)carbamate. InChi Key: MURCDOXDAHPNRQ-ZJKZPDEISA-N InChi Code: InChI=1S/C39H52N4O6/c1-26(2)21-33(37(47)41-32(35(40)45)24-29-19-13-8-14-20-29)42-36(46)30(22-27-15-9-6-10-16-27)25-34(44)31(23-28-17-11-7-12-18-28)43-38(48)49-39(3,4)5/h6-20,26,30-34,44H,21-25H2,1-5H3,(H2,40,45)(H,41,47)(H,42,46)(H,43,48)/t30-,31+,32+,33+,34-/m1/s1 SMILES Code: O=C(OC(C)(C)C)N[C@H]([C@H](O)C[C@@H](CC1=CC=CC=C1)C(N[C@@H](CC(C)C)C(N[C@@H](CC2=CC=CC=C2)C(N)=O)=O)=O)CC3=CC=CC=C3
Synonyms	L685458; L685,458; L-685,458; L 685,458; L-685458; L 685458;

实验参考方法

In Vitro	In vitro activity: L-685,458 inhibits Aβ(40) formation in both Neuro2A and CHO cell lines overexpressing human AβPP695, and in SHSY5Y cells overexpressing the construct spβA4CTF with IC50 of 402 nM, 113 nM, and 48 nM, respectively, with the potency for reduction of Aβ(42) being about 2-fold lower. In Tca8113 cells, L-685,458 inhibits cell growth by inducing G0–G1 cell cycle arrest and apoptosis. In a T-cell acute lymphoblastic leukemia cell line, pre-treatment with L-685,458 enhances the anti-proliferative effect of imatinib. L685,458 also significantly reduces HSV-1 replication in tissue culture by inhibiting signal peptide peptidase (SPP). Cell Assay: It is a pan-inhibitor of γ-secretase which decrease the products of Aβ(42) and Aβ(40) peptides. It displays a selectivity of 50-fold or greater inhibition than a range of aspartyl, serine, and cysteine protease in vitro membrane assay. L-685,458 reduced the product both total Aβand Aβ42 in human primary neuronal cells with IC50 value of 115 nM for Aβand Aβ42 for 200 nM[2]. L-685,458 also inhibitedγ-secretase activity by characterizing the production of total secreted Aβ?by ELISA with IC50 value of about 5 nM in HEK 293 cells overexpressing human APP751.
In Vivo	L-685,458 reduced the cortical total Aβwith a 50% reduction occurring at 100 mg/kg in a dose-dependent manner in PDAPP, and similar reductions in cortical Aβ42 were observed. L-685,458 decreased brain levels of Aβwhen given orally to Tg2576 mice that are transgenic for human APPV717F mutation. L-685,458 also inhibit the Notch signaling, then affects embryonic development in zebrafish embryos.
Animal model	Mouse model
Formulation & Dosage	10 mg/kg; p.o.
References	Biochemistry. 2000 Aug 1;39(30):8698-704; J Neurochem. 2001 Jan;76(1):173-81; J Pharmacol Exp Ther. 2003 Jun;305(3):864-71.

生物活性

Effects of DAPT (10, 30, and 100 mg/kg s.c.) on Brain and Plasma Aβ Levels in Young Tg2576 Mice. J Pharmacol Exp Ther. 2003 Jun;305(3):864-71.	Effects of DAPT (10, 30, and 100 mg/kg s.c.) on Brain, CSF, and Plasma Aβ Levels in Aged Tg2576 Mice. J Pharmacol Exp Ther. 2003 Jun;305(3):864-71.	Effects of acute p.o. DAPT administration on Aβ levels in the cortex and hippocampus in young (A and B) and old (C and D) Tg2576 mice. J Pharmacol Exp Ther. 2003 Jun;305(3):864-71.
Effects of acute p.o. DAPT administration on CSF (A and B) and plasma (C and D) Aβ. J Pharmacol Exp Ther. 2003 Jun;305(3):864-71.