LY411575

製品コードS2714 バッチS271403

化学情報

	Synonyms	N/A	Storage (From the date of receipt)	3 years -20°C powder 1 years -80°C in solvent
	化学式	C₂₆H₂₃F₂N₃O₄
	分子量	479.48	CAS No.	209984-57-6
Solubility (25°C)*	体外	DMSO	95 mg/mL (198.13 mM)
		Ethanol	13 mg/mL (27.11 mM)
		Water	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	LY411575は、強力なGamma-secretase阻害剤で、IC50は0.078 nM/0.082 nM（膜/細胞ベース）です。また、APPまたはNΔEを発現するHEK293細胞において、Notch切断をIC50 0.39 nMで阻害します。LY411575はapoptosisを誘導します。
in vitro	LY-411575 inhibits γ-secretase which can be assessed by the substrates like amyloid precursor protein (APP) and Notch S3 cleavage. This compound, which blocks Notch activation, results in apoptosis in primary and immortalized KS cells.
in vivo	10 mg/kg oral dose of LY-411575 decreases brain and plasma Aβ40 and -42 dose-dependently. This compound reduces cortical Aβ40 in young (preplaque) transgenic CRND8 mice (ED50 ≈ 0.6 mg/kg) and produces significant thymus atrophy and intestinal goblet cell hyperplasia at higher doses (>3 mg/kg). The therapeutic window is similar after oral and subcutaneous administration and in young and aged CRND8 mice. Both the thymus and intestinal side effects are reversible after a 2-week washout period. Three-week treatment with 1 mg/kg of this chemical reduces cortical Aβ40 by 69% without inducing intestinal effects, although a previously unreported change in coat color is observed.

プロトコル(参考用のみ)

キナーゼアッセイ	Assays for Aβ and NICD
キナーゼアッセイ	Procedures for measuring γ-secretase activity in membranes prepared from HEK293 cells expressing APP have been described previously (Zhang L et al Biochemistry 40, 5049-5055). Intact HEK293 cells expressing either APP or NΔE are treated with various concentrations of this compound for 4 hours at 37 °C. In the case of cells expressing NΔE, cells are lysed, the cell lysates are separated on a 4-12% NuPAGE gel, and the processed NICD fragment is detected via Western blot with a cleavage site-specific antibody. The inhibition of NICD production is quantified by spot densitometric analysis using FluorChem. In the case of cells expressing APP, the conditioned medium is collected, centrifuged at 10,000 × g for 5 minutes to remove cell debris, and stored at -20 °C prior to the determination of Aβ levels. Aβ40 and -42 produced in HEK293 membrane- and cell-based assays, as well as plasma Aβ40 and cortex Aβ40 from TgCRND8 mice, are analyzed without pretreatment using an electrochemiluminescence detection-based immunoassay. Plasma Aβ42 is measured by enzyme-linked immunosorbent assay. A commercially available enzyme-linked immunosorbent assay kit is used to measure cortex Aβ42 according to the manufacturer's instructions.
細胞アッセイ	細胞株	primary and immortalized KS cells
	濃度	500 μM
	反応時間	24 hours
	実験の流れ	DNA/PI staining is performed using standard methodologies. Briefly, 1 × 10⁶ cells are permeabilized with 100% ethanol in the presence of 15% FBS. The cells are washed and then treated for 15 minutes at 37 °C with 10 mg/mL RNAse. PI (5 mg/mL) is added, and the cells incubated for 1 hour at 4 °C prior to analysis by flow cytometry with 10 000 cells analysed per gated determination. The results are confirmed using the Immunotech Annexin V staining kit following the manufacturers’ instructions. At least three independent experiments are performed showing similar results.
動物実験	動物モデル	TgCRND8 mice model
	投薬量	1-10 mg/kg
	投与方法	Orally

参考

https://pubmed.ncbi.nlm.nih.gov/14709552/
https://pubmed.ncbi.nlm.nih.gov/15940249/
https://pubmed.ncbi.nlm.nih.gov/16946102/

カスタマーフィードバック

: Data from [Data independently produced by , , Exp Cell Res, 2017, 359(2):384-393]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes [ Nat Commun, 2025, 16(1):5913]	PubMed: 40659618
Mechanochemical coupling of cell shape and organ function optimizes heart size and contractile efficiency in zebrafish [ Dev Cell, 2025, S1534-5807(25)00468-X]	PubMed: 40774252
Age-dependent glial heterogeneity and traumatic injury responses in a vertebrate brain structure [ Cell Rep, 2025, 44(4):115508]	PubMed: 40198221
Single-nucleus profiling of mouse inner ear aging uncovers cell type heterogeneity and hair cell subtype-specific age-related signatures [ Cell Rep, 2025, 44(6):115781]	PubMed: 40440168
Distinct mechanisms regulate ventricular and atrial chamber wall formation [ Nat Commun, 2024, 15(1):8159]	PubMed: 39289341
The Notch-PDGFRβ axis suppresses brown adipocyte progenitor differentiation in early post-natal mice [ Dev Cell, 2024, 59(10):1233-1251.e5]	PubMed: 38569546
Tolerable glycometabolic stress boosts cancer cell resilience through altered N-glycosylation and Notch signaling activation [ Cell Death Dis, 2024, 15(1):53]	PubMed: 38225221
Akt3 activation by R-Ras in an endothelial cell enforces quiescence and barrier stability of neighboring endothelial cells via Jagged1 [ Cell Rep, 2024, 43(3):113837]	PubMed: 38402584
SOX10 mediates glioblastoma cell-state plasticity [ EMBO Rep, 2024, 10.1038/s44319-024-00258-8]	PubMed: 39285246
Molecular mechanism underlying miR-204-5p regulation of adipose-derived stem cells differentiation into cells from three germ layers [ Cell Death Discov, 2024, 10(1):95]	PubMed: 38388551

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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