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CAS No.: 292632-98-5

L-685458 Catalog No. CSN17284

Synonyms: L-685458L-685458;γ-Secretase Inhibitor X;L-685,458

L-685458 is an inhibitor of amyloid β-protein precursor gamma-secretase activity with Ki of 17 nM.

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400-920-2911

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实验方案

技术信息

生物活性

描述L-685458 is a structurally novel inhibitor of AβPP γ-secretase activity with IC50 value of 17nM for SHSY5Y spβA4CTF in vitro membrane assay of Aβ formation. L-685458 showed high selectivity against AβPP γ-secretase activity with much less potency to aspartyl, serine, and cysteine protease activity. Treatment with L-685458 dose-dependently inhibited Aβ40/42 formation in both Neuro2A and CHO cell lines overexpressing human AβPP695, and in SHSY5Y cells overexpressing the construct spβA4CTF with IC50 values of 402nM/775nM, 113nM/248nM and 48/67nM, respectively. Treatment with 10μM L-685458 for 18h almost completely inhibited Aβ and p3 secreted into the medium in HEK293 cells overexpressing human AβPP695 with a marked accumulation in the cell lysates of p3CTF and a lesser extent βCTF. Compared with γ-secretase inhibitor such as semagacestat, L-685458 works as a “ture-γ-secretase inhibitor” with decrease of intracellular byproduct peptides (produced along with Aβ through serial γ-cleavage of βAPP), intracellular Aβ and secreted Aβ in vivo, compared with semagacestat leading increase of both byproducts and intracellular Aβ.
作用机制L-685458 is an aspartyl protease transition state mimic which exhibits stereoselectivity to AβPP γ-secretase activity with much less potency to aspartyl, serine, and cysteine protease activity, thereby abolishing the formation of all Aβ peptide species.^[1]
动物研究
剂量
Mice: 1 mg/kg^[3] (i.p.)

给药途径
i.p.
参考文献

动物研究
剂量	Mice: 1 mg/kg^[3] (i.p.)
给药途径	i.p.

[1] Shearman MS, Beher D, et al. L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity. Biochemistry. 2000 Aug 1;39(30):8698-704.
[2] Tagami S, Yanagida K, et al. Semagacestat Is a Pseudo-Inhibitor of γ-Secretase. Cell Rep. 2017 Oct 3;21(1):259-273.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 1.4862 mL
- 7.4310 mL
- 14.8621 mL
- 5 mM
- 0.2972 mL
- 1.4862 mL
- 2.9724 mL
- 10 mM
- 0.1486 mL
- 0.7431 mL
- 1.4862 mL

技术信息

CAS号

292632-98-5

储存条件

粉末: Sealed in dry,Store in freezer, under -20°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C39H52N4O6

运输

蓝冰

分子量

672.85

别名

L-685458L-685458;γ-Secretase Inhibitor X;L-685,458

溶解度

DMSO	50.0 mg/mL (74.3 mM)
Water	insoluble

动物实验配方

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