產(chǎn)品目錄

規(guī)格	1mg 5mg
CAS	292632-98-5
別名
化學(xué)名	tert-butyl N-[(2S,3R,5R)-6-[[(2S)-1-[[(2S)-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
分子式	C39H52N4O6
分子量	672.85
溶解度	≥ 33.65mg/mL in DMSO
儲存條件	Store at -20°C
General tips	For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping Condition	Evaluation sample solution : ship with blue ice All other available size: ship with RT , or blue ice upon request

產(chǎn)品描述：

L-685,458 is a selective and Potent inhibitor of γ-secretase with IC50 value of 17 nM[1].

γ-Secretase is one of intramenbrane-cleaving aspartyl protease which cleaves many type-I membrane proteins and many of them have important biological functions. γ-Secretase is a multi-subunit protease and it contains presenilin, nicastrin, APH-1(Anterior Pharynx- defective 1) and PEN-2. Presenilin contains Asp258 and Asp385 embedded in the sixth and seventh transmembrane domain and forms the active site. The feature of being a membrane integrated protease complex makes it difficult to be purified as well as studying its mechanism. γ-secretase is responsible for the generation Aβfrom the amyloid precusor protein.? γ-Secretase has been considered as an important drug target for Alzheimer's disease. γ-Secertase also is responsible for Notch processing which is related to cancer such as leukemia.

L-685,458 is a transition state analogue inhibitor.

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.

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. [3] L-685,458 also inhibit the Notch signaling, then affects embryonic development in zebrafish embryos[4].

References:

1.Shearman MS, Beher D, Clarke EE, Lewis HD, Harrison T, Hunt P, Nadin A, Smith AL, Stevenson G, Castro JL: L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid beta-protein precursor gamma-secretase activity. Biochemistry 2000, 39(30):8698-8704.

2.Dovey HF, John V, Anderson JP, Chen LZ, de Saint Andrieu P, Fang LY, Freedman SB, Folmer B, Goldbach E, Holsztynska EJ et al: Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem 2001, 76(1):173-181.

3.Lanz TA, Himes CS, Pallante G, Adams L, Yamazaki S, Amore B, Merchant KM: The gamma-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester reduces A beta levels in vivo in plasma and cerebrospinal fluid in young (plaque-free) and aged (plaque-bearing) Tg2576 mice. J Pharmacol Exp Ther 2003, 305(3):864-871.

4.Geling A, Steiner H, Willem M, Bally-Cuif L, Haass C: A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish. EMBO Rep 2002, 3(7):688-694.

特別提醒：

1. 本產(chǎn)品僅供科研使用。請勿用于醫(yī)藥、臨床診斷或治療，食品及化妝品等用途。請勿存放于普通住宅區(qū)。

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原創(chuàng)作者：上海莼試生物技術(shù)有限公司

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