L-685458
Based on 6 publication(s) in Google Scholar
L-685458 is a potent transition state analog (TSA) γ-secretase inhibitor (GSI). L-685458 inhibits amyloid β-protein precursor γ-secretase activity with IC50 of 17 nM, shows greater than 50-100-fold selectivity over other aspartyl proteases tested. L685458 inhibits γ-secretase-mediated cleavage of APP-C99 and Notch-100 with IC50s of 301.3 nM and 351.3 nM, respectively. L-685458 can be used for the research of alzheimer’s disease (AD) and cancers.
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- Pureza: 99.48%
- No. CAS: 292632-98-5
- Fòrmula: C39H52N4O6
- Peso molecular:672.85
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Almacenamiento:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Actividad biológica
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Chemical Information
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Solvente y solubilidad
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Publications Citing Use of MedChemExpress (MCE) L-685458
More- Cell. 2021 Jan 21;184(2):521-533.e14. [Abstract]
- Cell Death Discov. 2025 Feb 23;11(1):76. [Abstract]
- Cell Rep. 2022 May 24;39(8):110857. [Abstract]
- Exp Cell Res. 2025 Jul 23;450(2):114677. [Abstract]
- Front Biosci (Landmark Ed). 2024 Feb 21;29(2):78. [Abstract]
- Evid Based Complement Alternat Med. 2018 Nov 21:2018:3082507. [Abstract]
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Actividad biológica
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | IC50 |
10 μM
Compound: L-685458
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Inhibition of SPP expressed in HEK293 cells in presence of Prl-PP peptide after 30 mins
Inhibition of SPP expressed in HEK293 cells in presence of Prl-PP peptide after 30 mins
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[PMID: 17932033] |
| HEK293 | IC50 |
10 nM
Compound: L-685458
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Displacement of [3H]L685458 from human SPP expressed in HEK293 cells
Displacement of [3H]L685458 from human SPP expressed in HEK293 cells
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[PMID: 17932033] |
| SH-SY5Y | IC50 |
115 nM
Compound: 3; L-658,458
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Inhibition of full-length human gamma secretase expressed in SH-SY5Y spbetaA4CTF cells assessed as reduction in amyloid beta levels after 90 mins by HTRF assay
Inhibition of full-length human gamma secretase expressed in SH-SY5Y spbetaA4CTF cells assessed as reduction in amyloid beta levels after 90 mins by HTRF assay
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[PMID: 27045975] |
| SH-SY5Y | IC50 |
22 nM
Compound: 1, L-685458
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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 |
281 nM
Compound: 1, L-685458
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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] |
| THP-1 | IC50 |
4.3 nM
Compound: L-685458
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Displacement of [3H]L685458 from gamma-secretase in human THP1 cells
Displacement of [3H]L685458 from gamma-secretase in human THP1 cells
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[PMID: 17932033] |
| THP-1 | IC50 |
72 nM
Compound: L-685458
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Displacement of [3H]IN973 from gamma-secretase in human THP1 cells
Displacement of [3H]IN973 from gamma-secretase in human THP1 cells
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[PMID: 17932033] |
L-685458 reduces both Aβ(40) and Aβ(42) peptide formation in 3 different cells. It against Neuro2A h AβPP695, CHO h AβPP695, and SHSY5 spβA4CTF reduction of Aβ(40) with IC50 values of 402 nM, 113 nM and 48 nM, respectively. And the IC50 values are 775 nM, 248 nM, 67 nM, respectively[1].L-685458 (5-40 μM; 24 hours) leads to a dramatic downregulation of Hes-1 in 786-O cells[3].L-685458 has inhibitory effects in hepatoma cell lines, it against Huh7, HepG2, HLE and SKHep1 cells with IC50 of 12.91 μM, 12.69 μM, 21.76 μM and 12.18 μM, respectively[4].
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.
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Animal Model:NOD-SCID Mouse Hepatoma Model[4]
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Dosage:5 mg/kg
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Administration:Percutaneous administration; 5 mg/kg; 2 weeks
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Result:Exhibited anti-tumor activities in vivo.
Chemical Information
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No. CAS 292632-98-5
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Appearance Solid
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Peso molecular 672.85
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Fòrmula C39H52N4O6
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Color White to off-white
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SMILES
O=C(N)[C@H](CC1=CC=CC=C1)NC([C@H](CC(C)C)NC([C@H](CC2=CC=CC=C2)C[C@@H](O)[C@@H](NC(OC(C)(C)C)=O)CC3=CC=CC=C3)=O)=O
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Synonyms
L-685,458
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (6)
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Journal Impact Factor
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Most Recent
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Cell
2021 Jan 21;184(2):521-533.e14. PMID: 33373587 -
Cell Death Discov
TDP43 is a newly identified substrate for PS1, enhancing the expression of APP following cleavage. [Abstract]2025 Feb 23;11(1):76. PMID: 39988698 -
Cell Rep
The epilepsy-associated protein PCDH19 undergoes NMDA receptor-dependent proteolytic cleavage and regulates the expression of immediate-early genes. [Abstract]2022 May 24;39(8):110857. PMID: 35613587 -
Exp Cell Res
PAI-1 regulates extracellular matrix remodeling and alters fibroblast profibrotic ability in skeletal muscle repair. [Abstract]2025 Jul 23;450(2):114677. PMID: 40712909 -
Front Biosci (Landmark Ed)
2024 Feb 21;29(2):78. PMID: 38420818 -
Evid Based Complement Alternat Med
Tetramethylpyrazine and Paeoniflorin Inhibit Oxidized LDL-Induced Angiogenesis in Human Umbilical Vein Endothelial Cells via VEGF and Notch Pathways. [Abstract]2018 Nov 21:2018:3082507. PMID: 30584451
L-685458 purchased from MedChemExpress. Usage Cited in: Evid Based Complement Alternat Med. 2018 Nov 21:2018:3082507. [Abstract]
Protein extracts are immunoblotted to determine the relative expression levels of VEGFR2, Notch1, Jagged1, and Hes1 in the treatment of Ox-LDL, TMP, PF, L-6854598.
Solvente y solubilidad
DMSO : 83.3 mg/mL (123.80 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
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)
Pureza y Documentación
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Ficha de datos (277 KB)
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SDS (254 KB)
- English - EN (254 KB)
- Français - FR (254 KB)
- Deutsch - DE (254 KB)
- Norwegian - NO (254 KB)
- Español - ES (254 KB)
- Swedish - SV (254 KB)
- Italian - IT (254 KB)
- Korean - KR (254 KB)
- Portuguese - PT (254 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Shearman, M.S., Beher, D., Clarke, E.E., Lewis, H.D., Harrison, T., Hunt, P., [Content Brief]
[2]. Guanghui Yang, et al. Structural basis of γ-secretase inhibition and modulation by small molecule drugs. Cell. 2021 Jan 21;184(2):521-533.e14. [Content Brief]
[3]. Jonas Sjölund, et al. Suppression of renal cell carcinoma growth by inhibition of Notch signaling in vitro and in vivo. J Clin Invest. 2008 Jan;118(1):217-28. [Content Brief]
[4]. Kazunori Kawaguchi, et al. Jagged1 DNA Copy Number Variation Is Associated with Poor Outcome in Liver Cancer. Am J Pathol. 2016 Aug;186(8):2055-2067. [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 | 1.4862 mL | 7.4311 mL | 14.8622 mL | 37.1554 mL |
| 5 mM | 0.2972 mL | 1.4862 mL | 2.9724 mL | 7.4311 mL | |
| 10 mM | 0.1486 mL | 0.7431 mL | 1.4862 mL | 3.7155 mL | |
| 15 mM | 0.0991 mL | 0.4954 mL | 0.9908 mL | 2.4770 mL | |
| 20 mM | 0.0743 mL | 0.3716 mL | 0.7431 mL | 1.8578 mL | |
| 25 mM | 0.0594 mL | 0.2972 mL | 0.5945 mL | 1.4862 mL | |
| 30 mM | 0.0495 mL | 0.2477 mL | 0.4954 mL | 1.2385 mL | |
| 40 mM | 0.0372 mL | 0.1858 mL | 0.3716 mL | 0.9289 mL | |
| 50 mM | 0.0297 mL | 0.1486 mL | 0.2972 mL | 0.7431 mL | |
| 60 mM | 0.0248 mL | 0.1239 mL | 0.2477 mL | 0.6193 mL | |
| 80 mM | 0.0186 mL | 0.0929 mL | 0.1858 mL | 0.4644 mL | |
| 100 mM | 0.0149 mL | 0.0743 mL | 0.1486 mL | 0.3716 mL |
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