LY-411575
Based on 28 publication(s) in Google Scholar
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 an IC50 of 0.39 nM.
For research use only. We do not sell to patients.
- Purity: 98.68%
- CAS No.: 209984-57-6
- Formula: C26H23F2N3O4
- Molecular Weight:479.48
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Apoptosis Compound Library
HY-L003
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Immunology/Inflammation Compound Library
HY-L007
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Neuronal Signaling Compound Library
HY-L013
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Stem Cell Signaling Compound Library
HY-L017
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Wnt/Hedgehog/Notch Compound Library
HY-L020
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Anti-Cancer Compound Library
HY-L025
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Anti-Aging Compound Library
HY-L034
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Differentiation Inducing Compound Library
HY-L038
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Reprogramming Compound Library
HY-L039
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Anti-Breast Cancer Compound Library
HY-L074
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Anti-Pancreatic Cancer Compound Library
HY-L077
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Neurodegenerative Disease-related Compound Library
HY-L086
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Angiogenesis-Related Compound Library
HY-L088
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Transcription Factor-Targeted Library
HY-L090
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Anti-Liver Cancer Compound Library
HY-L101
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Anti-Colorectal Cancer Compound Library
HY-L103
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Cancer Stem Cells Compound Library
HY-L135
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Membrane Protein-targeted Compound Library
HY-L149
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Cell Death Library
HY-L162
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Multi-Target Compound Library
HY-L176
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Bioactive Compound Library Max
HY-L181
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Anti-Aging Compound Library Mini
HY-L034M
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MCE Bioactive Compound Library
HY-L001V
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Bioactive Compound Library
HY-L001
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Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library
HY-L199
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Cell Proliferation Compound Library
HY-L201
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High-Throughput Bioactive Compound Library
HY-L205
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Anti-Rheumatic Arthritis Compound Library
HY-L210
Publications Citing Use of MedChemExpress (MCE) LY-411575
More- Nat Commun. 2026 Jun 19. [Abstract]
- Nat Commun. 2025 Aug 27;16(1):7979. [Abstract]
- Adv Sci (Weinh). 2022 Sep 18;e2203557. [Abstract]
- Cell Death Dis. 2022 Jan 17;13(1):60. [Abstract]
- Proc Natl Acad Sci U S A. 2025 Feb 25;122(8):e2421573122. [Abstract]
- Cell Rep. 2016 Dec 6;17(10):2687-2699. [Abstract]
- Oncoimmunology. 2018 Aug 23;7(11):e1461303. [Abstract]
- Chin J Nat Med. 2024 Nov;22(11):991-1002. [Abstract]
- Int Immunopharmacol. 2022 Sep 28;112:109251. [Abstract]
- Molecules. 2013 Sep 3;18(9):10747-67. [Abstract]
- BMC Biol. 2015 Sep 2;13(1):70. [Abstract]
- BMC Biol. 2013 Jul 8;11:78. [Abstract]
- J Virol. 2024 Nov 12:e0121624. [Abstract]
- Mol Biol Rep. 2024 Nov 8;51(1):1134. [Abstract]
- J Steroid Biochem Mol Biol. 2025 Mar:247:106669. [Abstract]
- Biochem Biophys Res Commun. 2025 Dec 2:794:153091. [Abstract]
- Exp Neurobiol. 2020 Dec 31;29(6):417-424. [Abstract]
- bioRxiv. 2025 Sep 9.
- bioRxiv. 2025 Aug 12.
- bioRxiv. 2025 Apr 19:2025.04.18.649014. [Abstract]
- Res Sq. 2025 Feb 23.
- bioRxiv. 2025 January 09.
- bioRxiv. 2024 October 29.
- bioRxiv. 2023 Jun 12.
- Curr Res Pharmacol Drug Discov. 2022 Jul 4:3:100117. [Abstract]
- ACS Comb Sci. 2019 Dec 9;21(12):805-816. [Abstract]
- Goethe University. 2019 Dec.
- University of Liege. Septembre. 2015.
Customer Validation & Images
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WB
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IF
Biological Activity
IC50: 0.078 nM (γ-secretase in membrane), 0.082 nM (γ-secretase cell-based), 0.39 nM (Notch S3 cleavage cell-based)[1]
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CHO | EC50 |
114 pM
Compound: LY-411575
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Reduction of human wild type PS1-induced amyloid beta-40 level in CHO cells overexpressing human APP751 after 24 hrs by liquid phase electrochemiluminescence assay relative to control
Reduction of human wild type PS1-induced amyloid beta-40 level in CHO cells overexpressing human APP751 after 24 hrs by liquid phase electrochemiluminescence assay relative to control
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[PMID: 17573346] |
| CHO | EC50 |
135 pM
Compound: LY-411575
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Reduction of human wild type PS1-induced amyloid beta-42 level in CHO cells overexpressing human APP751 after 24 hrs by liquid phase electrochemiluminescence assay relative to control
Reduction of human wild type PS1-induced amyloid beta-42 level in CHO cells overexpressing human APP751 after 24 hrs by liquid phase electrochemiluminescence assay relative to control
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[PMID: 17573346] |
| CHO | EC50 |
352 pM
Compound: LY-411575
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Reduction of human PS1 delta exon9 mutant-induced amyloid beta-42 level in CHO cells overexpressing human APP751after 24 hrs by liquid phase electrochemiluminescence assay relative to control
Reduction of human PS1 delta exon9 mutant-induced amyloid beta-42 level in CHO cells overexpressing human APP751after 24 hrs by liquid phase electrochemiluminescence assay relative to control
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[PMID: 17573346] |
| CHO | EC50 |
358 pM
Compound: LY-411575
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Reduction of human PS1 delta exon9 mutant-induced amyloid beta-40 level in CHO cells overexpressing human APP751after 24 hrs by liquid phase electrochemiluminescence assay relative to control
Reduction of human PS1 delta exon9 mutant-induced amyloid beta-40 level in CHO cells overexpressing human APP751after 24 hrs by liquid phase electrochemiluminescence assay relative to control
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[PMID: 17573346] |
| HEK293 | EC50 |
119 pM
Compound: LY-411575
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Inhibition of gamma secretase in human HEK293 cells assessed as amyloid beta 40 production
Inhibition of gamma secretase in human HEK293 cells assessed as amyloid beta 40 production
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[PMID: 17573346] |
| HEK293 | IC50 |
1.2 μM
Compound: LY411575
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Modulation of gamma-secretase in HEK293 cells expressing guinea pig Swedish mutant SFV-APP695sw coexpressing DLL4 assessed as inhibition of notch processing in human TE671 cells after 3 days by dual-cell luciferase reporter gene assay
Modulation of gamma-secretase in HEK293 cells expressing guinea pig Swedish mutant SFV-APP695sw coexpressing DLL4 assessed as inhibition of notch processing in human TE671 cells after 3 days by dual-cell luciferase reporter gene assay
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[PMID: 24139583] |
| HEK293 | IC50 |
0.08 nM
Compound: 19; LY-411575
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Inhibition of gamma secretase in HEK293 cells expressing APP 695 assessed as reduction in amyloid beta levels after 5 hrs by Western blot analysis
Inhibition of gamma secretase in HEK293 cells expressing APP 695 assessed as reduction in amyloid beta levels after 5 hrs by Western blot analysis
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[PMID: 27045975] |
| HEK293 | IC50 |
0.39 nM
Compound: 19; LY-411575
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Inhibition of gamma secretase mediated Notch signaling in HEK293 cells after 5 hrs by Western blot analysis
Inhibition of gamma secretase mediated Notch signaling in HEK293 cells after 5 hrs by Western blot analysis
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[PMID: 27045975] |
| HEK293 | IC50 |
0.01 μM
Compound: 42; LY-411,575
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Inhibition of human SPPL2a expressed in HEK293 cells using GAL4-VP16 fusedTNFalpha (1 to 76)-NTF as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay
Inhibition of human SPPL2a expressed in HEK293 cells using GAL4-VP16 fusedTNFalpha (1 to 76)-NTF as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay
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[PMID: 29359565] |
| HEK293 | IC50 |
<0.0003 μM
Compound: 42; LY-411,575
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Inhibition of human gamma-secretase expressed in HEK293 cells using Notch1-VP16-Gal4 as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay
Inhibition of human gamma-secretase expressed in HEK293 cells using Notch1-VP16-Gal4 as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay
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[PMID: 29359565] |
| HEK293 | IC50 |
<0.3 nM
Compound: 42; LY-411,575
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Inhibition of human gamma-secretase expressed in HEK293 cells using Notch1-VP16-Gal4 as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay
Inhibition of human gamma-secretase expressed in HEK293 cells using Notch1-VP16-Gal4 as substrate after 24 hrs by Bright-Glo luciferase reporter gene assay
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[PMID: 29359565] |
| Huh-7 | IC50 |
80 μM
Compound: 118, LY-411575
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Antimalarial activity against Plasmodium berghei ANKA infected in human Huh7 cells after 24 hrs by qRT-PCR
Antimalarial activity against Plasmodium berghei ANKA infected in human Huh7 cells after 24 hrs by qRT-PCR
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[PMID: 22122518] |
| SH-SY5Y | IC50 |
1 nM
Compound: 15 LY-411575
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Displacement of [3H]5-chloro-N-((2S,3R)-5,5,5-trifluoro-1-hydroxy-3-methylpentan-2-yl)thiophene-2-sulfonamide from gamma secretase in human SH-SY5Y cells by competitive binding assay
Displacement of [3H]5-chloro-N-((2S,3R)-5,5,5-trifluoro-1-hydroxy-3-methylpentan-2-yl)thiophene-2-sulfonamide from gamma secretase in human SH-SY5Y cells by competitive binding assay
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[PMID: 19694467] |
| SH-SY5Y | IC50 |
1 nM
Compound: 15 LY-411575
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Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in human SH-SY5Y cells
Inhibition of gamma secretase-mediated amyloid beta (1 to 40) production in human SH-SY5Y cells
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[PMID: 19694467] |
LY-411575 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 BMS-790052 (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].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 209984-57-6
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Appearance Solid
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Molecular Weight 479.48
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Formula C26H23F2N3O4
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Color White to off-white
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SMILES
O=C1[C@@H](NC([C@@H](NC([C@H](C2=CC(F)=CC(F)=C2)O)=O)C)=O)C3=CC=CC=C3C(C=CC=C4)=C4N1C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (28)
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Journal Impact Factor
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Most Recent
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Nat Commun
Notch coordinates self-organization of germ layers and axial polarity in sea anemone gastruloids. [Abstract]2026 Jun 19. PMID: 42321198 -
Nat Commun
Segregation of endoderm and mesoderm germ layer identities in the diploblast Nematostella vectensis. [Abstract]2025 Aug 27;16(1):7979. PMID: 40858588 -
Adv Sci (Weinh)
Ti3 C2 Tx MXene Composite 3D Hydrogel Potentiates mTOR Signaling to Promote the Generation of Functional Hair Cells in Cochlea Organoids. [Abstract]2022 Sep 18;e2203557. PMID: 36117048 -
Cell Death Dis
2022 Jan 17;13(1):60. PMID: 35039472 -
Proc Natl Acad Sci U S A
Druggable genome screens identify SPP as an antiviral host target for multiple flaviviruses. [Abstract]2025 Feb 25;122(8):e2421573122. PMID: 39969998 -
Cell Rep
In Vivo Visualization of Cardiomyocyte Apicobasal Polarity Reveals Epithelial to Mesenchymal-like Transition during Cardiac Trabeculation. [Abstract]2016 Dec 6;17(10):2687-2699. PMID: 27926871 -
Oncoimmunology
Th17 cell-derived IL-17A promoted tumor progression via STAT3/NF-κB/Notch1 signaling in non-small cell lung cancer. [Abstract]2018 Aug 23;7(11):e1461303. PMID: 30377557
LY-411575 purchased from MedChemExpress. Usage Cited in: Oncoimmunology. 2018 Aug 23;7(11):e1461303. [Abstract]
The expression of Oct4 in A549 and H460 cells treated with or without rhIL-17A and these molecular inhibitors (NF-kB inhibitor: PDAC, Notch1 inhibitor: LY411575) are assessed by western blotting.
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Chin J Nat Med
Luteolin ameliorates ulcerative colitis in mice via reducing the depletion of NCR+ILC3 through Notch signaling pathway. [Abstract]2024 Nov;22(11):991-1002. PMID: 39510641 -
Int Immunopharmacol
Luteolin alleviates ulcerative colitis by restoring the balance of NCR-ILC3/NCR+ILC3 to repairing impaired intestinal barrier. [Abstract]2022 Sep 28;112:109251. PMID: 36182875 -
Molecules
New flurbiprofen derivatives: synthesis, membrane affinity and evaluation of in vitro effect on β-amyloid levels. [Abstract]2013 Sep 3;18(9):10747-67. PMID: 24005968 -
BMC Biol
Progenitor potential of nkx6.1-expressing cells throughout zebrafish life and during beta cell regeneration. [Abstract]2015 Sep 2;13(1):70. PMID: 26329351
LY-411575 purchased from MedChemExpress. Usage Cited in: BMC Biol. 2015 Sep 2;13(1):70. [Abstract]
Short-term lineage tracing: immunodetection of GFP and the Ins and Gcg hormones in 5-dpf Tg(ascl1b:eGFP-creER T2 ) embryos treated from 3 to 5 dpf with DMSO or with the Notch signaling inhibitor, LY411575.
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BMC Biol
Ascl1b and Neurod1, instead of Neurog3, control pancreatic endocrine cell fate in zebrafish. [Abstract]2013 Jul 8;11:78. PMID: 23835295 -
J Virol
SRCAP is involved in porcine reproductive and respiratory syndrome virus activated Notch signaling pathway. [Abstract]2024 Nov 12:e0121624. PMID: 39530666 -
Mol Biol Rep
2024 Nov 8;51(1):1134. PMID: 39514048 -
J Steroid Biochem Mol Biol
Segetalin B promotes bone formation in ovariectomized mice by activating PLD1/SIRT1 signaling to inhibit γ-secretase-mediated Notch1 overactivation. [Abstract]2025 Mar:247:106669. PMID: 39736459 -
Biochem Biophys Res Commun
Establishment of γ-secretase-deficient goblet-like cells: A novel in vitro platform to dissect regulatory mechanisms of mucus production in the intestinal epithelium. [Abstract]2025 Dec 2:794:153091. PMID: 41344214 -
Exp Neurobiol
Notch Signaling Controls Oligodendrocyte Regeneration in the Injured Telencephalon of Adult Zebrafish. [Abstract]2020 Dec 31;29(6):417-424. PMID: 33281119 -
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bioRxiv
Tnfrsf10 Signaling is Required to Maintain the Stem Cell Niche in the Zebrafish Lateral Line. [Abstract]2025 Apr 19:2025.04.18.649014. PMID: 40568085 -
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Curr Res Pharmacol Drug Discov
Jagged-1 is induced by mTOR inhibitors in renal cancer cells through an Akt/ALK5/Smad4-dependent mechanism. [Abstract]2022 Jul 4:3:100117. PMID: 35992379 -
ACS Comb Sci
Benzimidazolyl-pyrazolo[3,4- b]pyridinones, Selective Inhibitors of MOLT-4 Leukemia Cell Growth and Sea Urchin Embryo Spiculogenesis: Target Quest. [Abstract]2019 Dec 9;21(12):805-816. PMID: 31689077 -
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Solvent & Solubility
DMSO : ≥ 100 mg/mL (208.56 mM; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.21 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocol
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.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (283 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
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. [Content Brief]
[2]. 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 [Content Brief]
[3]. 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. [Content Brief]
[4]. 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. [Content Brief]
[5]. 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. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.0856 mL | 10.4280 mL | 20.8559 mL | 52.1398 mL |
| 5 mM | 0.4171 mL | 2.0856 mL | 4.1712 mL | 10.4280 mL | |
| 10 mM | 0.2086 mL | 1.0428 mL | 2.0856 mL | 5.2140 mL | |
| 15 mM | 0.1390 mL | 0.6952 mL | 1.3904 mL | 3.4760 mL | |
| 20 mM | 0.1043 mL | 0.5214 mL | 1.0428 mL | 2.6070 mL | |
| 25 mM | 0.0834 mL | 0.4171 mL | 0.8342 mL | 2.0856 mL | |
| 30 mM | 0.0695 mL | 0.3476 mL | 0.6952 mL | 1.7380 mL | |
| 40 mM | 0.0521 mL | 0.2607 mL | 0.5214 mL | 1.3035 mL | |
| 50 mM | 0.0417 mL | 0.2086 mL | 0.4171 mL | 1.0428 mL | |
| 60 mM | 0.0348 mL | 0.1738 mL | 0.3476 mL | 0.8690 mL | |
| 80 mM | 0.0261 mL | 0.1303 mL | 0.2607 mL | 0.6517 mL | |
| 100 mM | 0.0209 mL | 0.1043 mL | 0.2086 mL | 0.5214 mL |
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