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209984-57-6

209984-57-6 structure
209984-57-6 structure
  • Name: LY-411575
  • Chemical Name: ly-411575
  • CAS Number: 209984-57-6
  • Molecular Formula: C26H23F2N3O4
  • Molecular Weight: 479.475
  • Catalog: Biochemical Inhibitor Proteases Gamma-secretase inhibitor
  • Create Date: 2018-10-11 23:19:19
  • Modify Date: 2024-01-13 13:56:25
  • LY-411575 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), and also inhibits Notch S3 cleavage with IC50 of 0.39 nM.
Name ly-411575
Synonyms N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide
Benzeneacetamide, N-[(1S)-2-[[(7S)-6,7-dihydro-5-methyl-6-oxo-5H-dibenz[b,d]azepin-7-yl]amino]-1-methyl-2-oxoethyl]-3,5-difluoro-α-hydroxy-, (αS)-
N-[(2S)-2-(3,5-Difluorophenyl)-2-hydroxyacetyl]-N-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide
(2S)-2-[[(2S)-2-(3,5-difluorophenyl)-2-hydroxyacetyl]amino]-N-[(7S)-5-methyl-6-oxo-7H-benzo[d][1]benzazepin-7-yl]propanamide
cc-581
LY411575
Description LY-411575 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), and also inhibits Notch S3 cleavage with IC50 of 0.39 nM.
Related Catalog
Target

IC50: 0.078 nM (γ-secretase in membrane), 0.082 nM (γ-secretase cell-based), 0.39 nM (Notch S3 cleavage cell-based)[1]

In Vitro LY-411,575 blocks Notch activation, and results in apoptosis in primary and immortalized KS cells. LY-411,575 (500 μM) induces G2/M growth arrest SLK cells[2]. LY411575 treatment significantly decreases the amounts of intracellular HCV RNA with IC50 of 0.56 ± 0.20 μM and extracellular HCV particles. LY411575 (0-40 nM) alone or in combination with daclatasvir (0-40 pM) decreases supernatant infectious titers in a dose-dependent manner, and is synergistic regarding production of infectious virus. LY411575 (10 µM) treatment impairs ROS production in HCVcc-infected cells[4]. LY411575 significantly attenuates EMT by inhibiting the Notch signaling activation in vitro[5].
In Vivo LY-411,575 (10 mg/kg) decreases brain and plasma Aβ40 and -42 robustly when chronically administered to TgCRND8 mice[1]. LY411,575 reduces cortical Aβ40 in young transgenic CRND8 mice (ED50 appr 0.6 mg/kg) and produces significant thymus atrophy and intestinal goblet cell hyperplasia at higher doses (>3 mg/kg). The extent of intestinal goblet cell hyperplasia induced by LY411,575 (10 mg/kg) is similar in young and aged mice[3]. LY411575 inhibits mouse proliferative vitreoretinopathy (PVR) formation in vivo[5].
Animal Admin Mice from the aged cohort (16-26 months old) are either retired breeders or experimentally naive mice. Before dosing begin and for the duration of the study, mice are singly housed with a plastic igloo and nesting material. Mice are sacrificed 2 to 4 h after their final dosing. For oral dosing, LY411,575 and LY-D are formulated as 10 mg/mL solutions and diluted 1:10 with 0.4% methycellulose. In the case of subcutaneous dosing, the 10 mg/mL stock solution is diluted 1:10 with 20% hydroxyl-propyl-β-cyclodextrin. If necessary, serial dilutions are made from the 1 mg/mL solution using the appropriate 1:10 vehicle. The dosing volume is 10 mL/kg. After oral administration of 10 mg/kg LY411,575, inhibition of plasma Aβ is still significant 24, but not 48, h after dosing, so in an effort to maintain continuous γ-secretase inhibition, LY411,575 and LY-D are dosed once per day in all studies.
References

[1]. Wong GT, et al. Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem. 2004 Mar 26;279(13):12876-82.

[2]. Curry CL, et al. Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi's sarcoma tumor cells. Oncogene. 2005 Sep 22;24(42):6333-44.

[3]. Hyde LA, et al. Studies to investigate the in vivo therapeutic window of the gamma-secretase inhibitor N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide (LY411,575) in the CRND8 mouse. J Pharmacol Exp Ther. 2006 Dec;319(3):1133-43.

[4]. Otoguro T, et al. Inhibitory effect of presenilin inhibitor LY411575 on maturation of hepatitis C virus core protein, production of the viral particle and expression of host proteins involved in pathogenicity. Microbiol Immunol. 2016 Nov;60(11):740-753

[5]. Zhang J, et al. Notch signaling modulates proliferative vitreoretinopathy via regulating retinal pigment epithelial-to-mesenchymal transition. Histochem Cell Biol. 2017 Mar;147(3):367-375.
Density 1.4±0.1 g/cm3
Boiling Point 836.0±65.0 °C at 760 mmHg
Melting Point 328.47°C
Molecular Formula C26H23F2N3O4
Molecular Weight 479.475
Flash Point 459.4±34.3 °C
Exact Mass 479.165649
PSA 98.74000
LogP 4.75
Appearance white to beige
Vapour Pressure 0.0±3.2 mmHg at 25°C
Index of Refraction 1.652
Storage condition ?20°C
Water Solubility DMSO: soluble5mg/mL, clear
Safety Phrases 24/25
RIDADR NONH for all modes of transport
HS Code 29337900

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title: CAS No. 209984-57-6 | Chemsrc address: https://www.chemsrc.com/en/baike/122802.html

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