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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L-685458 Chemical Structure
CAS No. : 292632-98-5
This product is a controlled substance and not for sale in your territory.
Based on 4 publication(s) in Google Scholar
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.
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Description
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[1][2].
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.
L-685458 Related Antibodies
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.
Room temperature in continental US; may vary elsewhere.
Stockage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
2 years
-20°C
1 year
Solvant et solubilité
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)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
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
View the 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.
[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]
[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.
[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.
[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.
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
ConcentrationSolventMass
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
L-685458 Related Classifications
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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