Art. -Nr.: HY-19369

L-685458

(Synonyms: L-685,458)

6 Cited Publications

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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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Reinheit: 99.48%
CAS. Nr.: 292632-98-5
Formel: C₃₉H₅₂N₄O₆
Molecular Weight:672.85

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year

L-685458 Chemical Structure

CAS. Nr.: 292632-98-5

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Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- Cellular Effect
- In Vitro
- In Vivo
Chemical Information
Publications (6)
Lösungsmittel & Löslichkeit
- In Vitro
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

Cellular Effect

Cell Line	Type	Value	Description	References
HEK293	IC₅₀	10 μM Compound: L-685458	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	[PMID: 17932033]
HEK293	IC₅₀	10 nM Compound: L-685458	Displacement of [3H]L685458 from human SPP expressed in HEK293 cells Displacement of [3H]L685458 from human SPP expressed in HEK293 cells	[PMID: 17932033]
SH-SY5Y	IC₅₀	115 nM Compound: 3; L-658,458	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	[PMID: 27045975]
SH-SY5Y	IC₅₀	22 nM Compound: 1, L-685458	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	[PMID: 19694467]
SH-SY5Y	IC₅₀	281 nM Compound: 1, L-685458	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	[PMID: 19694467]
THP-1	IC₅₀	4.3 nM Compound: L-685458	Displacement of [3H]L685458 from gamma-secretase in human THP1 cells Displacement of [3H]L685458 from gamma-secretase in human THP1 cells	[PMID: 17932033]
THP-1	IC₅₀	72 nM Compound: L-685458	Displacement of [3H]IN973 from gamma-secretase in human THP1 cells Displacement of [3H]IN973 from gamma-secretase in human THP1 cells	[PMID: 17932033]

In Vitro

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.

In Vivo

L-685458 (percutaneous administration; 5 mg/kg; 2 weeks) has antitumor effects in mouse hepatoma models. L-685458 inhibits EpCAM production except in necrotic areas. And HES1 staining is also diminished in the nucleus^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

NOD-SCID Mouse Hepatoma Model^[4]
Dosage:

5 mg/kg
Administration:

Percutaneous administration; 5 mg/kg; 2 weeks
Result:

Exhibited anti-tumor activities in vivo.

Chemical Information

CAS. Nr. 292632-98-5
Appearance Solid
Molecular Weight 672.85
Formel C₃₉H₅₂N₄O₆
Color White to off-white
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
Synonyms

L-685,458
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	2 years
	-20°C	1 year

Publications (6)

All WB

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Journal Impact Factor

Cell

Structural basis of γ-secretase inhibition and modulation by small molecule drugs. [Abstract]

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)

The Large Ectodomain of APP Prevents APP from being Directly Cleaved by γ-Secretase. [Abstract]

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.

Lösungsmittel & Löslichkeit

In Vitro:

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.4862 mL

7.4311 mL

14.8622 mL

5 mM

0.2972 mL

1.4862 mL

2.9724 mL

10 mM

0.1486 mL

0.7431 mL

1.4862 mL

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.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (277 KB)
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)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[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]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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

Keywords

L-685458

6 Cited Publications

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L-685458

Apoptosis Compound Library

Neuronal Signaling Compound Library

Stem Cell Signaling Compound Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Differentiation Inducing Compound Library

Reprogramming Compound Library

Anti-Alzheimer's Disease Compound Library

Neurodegenerative Disease-related Compound Library

Cancer Stem Cells Compound Library

Membrane Protein-targeted Compound Library

Cell Death Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

High-Throughput Bioactive Compound Library

Publications Citing Use of MedChemExpress (MCE) L-685458

Biologische Aktivität

Chemical Information

Publications (6)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

L-685458

Apoptosis Compound Library

Neuronal Signaling Compound Library

Stem Cell Signaling Compound Library

Anti-Cancer Compound Library

Anti-Aging Compound Library

Differentiation Inducing Compound Library

Reprogramming Compound Library

Anti-Alzheimer's Disease Compound Library

Neurodegenerative Disease-related Compound Library

Cancer Stem Cells Compound Library

Membrane Protein-targeted Compound Library

Cell Death Library

Bioactive Compound Library Max

MCE Bioactive Compound Library

Bioactive Compound Library

Non-Alcoholic Fatty Liver Disease (NAFLD) Compound Library

High-Throughput Bioactive Compound Library

Publications Citing Use of MedChemExpress (MCE) L-685458

Biologische Aktivität

Chemical Information

Publications (6)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

L-685458 Related Classifications

HY-19369 Related Classifications