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Biological Activity
Potent and selective γ-secretase inhibitor (IC50 = 17 nM) that displays > 50-fold selectivity over a range of aspartyl, serine and cysteine proteases. Exhibits equal potency for inhibition of Aβ40 and Aβ42 peptides (IC50 values are 48 and 67 nM respectively in human neuroblastoma cells). Also regulates CXCR4 and VEGFR2 expression through inhibition of Notch signaling in vitro.
Technical Data
| M. Wt | 672.85 |
| Formula | C39H52N4O6 |
| Storage | Store at -20°C |
| Purity | ≥97% (HPLC) |
| CAS Number | 292632-98-5 |
| PubChem ID | 5479543 |
| InChI Key | MURCDOXDAHPNRQ-ZJKZPDEISA-N |
| Smiles | O[C@H](C[C@@H](CC1=CC=CC=C1)C(N[C@@H](CC(C)C)C(N[C@@H](CC3=CC=CC=C3)C(N)=O)=O)=O)[C@H](CC2=CC=CC=C2)NC(OC(C)(C)C)=O |
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
All Tocris products are intended for laboratory research use only.
Solubility Data
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 10.09 | 15 |
Preparing Stock Solutions
The following data is based on the product molecular weight 672.85. Batch specific molecular weights may vary from batch to batch due to solvent of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.49 mL | 7.43 mL | 14.86 mL |
| 5 mM | 0.3 mL | 1.49 mL | 2.97 mL |
| 10 mM | 0.15 mL | 0.74 mL | 1.49 mL |
| 50 mM | 0.03 mL | 0.15 mL | 0.3 mL |
Molarity Calculator
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Product Datasheets
References
References are publications that support the products' biological activity.
Shearman et al (2000) L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of amyloid-β-protein precursor γ-secretase activity. Biochemistry 39 8698 PMID: 10913280
Williams et al (2006) Up-regulation of the Notch ligand delta-like 4 inhibits VEGF-induced endothelial cell function. Blood 107 931 PMID: 16219802
Williams et al (2008) Regulation of CXCR4 by the Notch ligand delta-like 4 in endothelial cells. Cancer Res. 68 1889 PMID: 18339870
Keywords: L-685,458, supplier, Potent, selective, γ-secretase, gamma-secretase, inhibitors, inhibits, Aβ4, beta40, β42, beta42, Proteinases, Proteases, b-amyloid, β-Amyloid, beta-Amyloid, Precursor, Protein, APP, beta, Peptides, L685458, amyloidbeta, amyloidb, amyloidβ, Gamma-Secretase, Amyloid, Beta, Peptides, Gamma-Secretase, Tocris Bioscience
