| Synonyms |
L-trans-Epoxysuccinyl(OEt)-Leu-3-methylbutylamide; L-trans-Epoxysuccinyl-Leu-3-methylbutylamide-ethyl ester; (2S,3S)-3-[[[(1S)-3-Methyl-1-[[(3-methylbutyl)amino]carbonyl]butyl]amino]carbonyl]-2-oxiranecarboxylic Acid Ethyl Ester; E 64c ethyl ester; E 64d; EP 453; EST; Loxistatin; NSC 694281; (2S,3S)-trans-Epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester |
| IUPAC Name |
ethyl (2S,3S)-3-[[(2S)-4-methyl-1-(3-methylbutylamino)-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylate |
| Molecular Weight |
342.43 |
| Molecular Formula |
C17H30N2O5 |
| Canonical SMILES |
CCOC(=O)C1C(O1)C(=O)NC(CC(C)C)C(=O)NCCC(C)C |
| InChI |
InChI=1S/C17H30N2O5/c1-6-23-17(22)14-13(24-14)16(21)19-12(9-11(4)5)15(20)18-8-7-10(2)3/h10-14H,6-9H2,1-5H3,(H,18,20)(H,19,21)/t12-,13-,14-/m0/s1 |
| InChIKey |
SRVFFFJZQVENJC-IHRRRGAJSA-N |
| Boiling Point |
538.0±50.0°C at 760 mmHg |
| Melting Point |
123-125°C |
| Flash Point |
238.4±31.5 °C |
| Purity |
98% |
| Density |
1.1±0.1 g/cm3 |
| Solubility |
Soluble in Chloroform (Slightly), Methanol (Slightly, Heated) |
| Appearance |
White Solid |
| Storage |
Store at -20°C |
| Animal Admin |
Mice and Guinea Pigs are used. Male transgenic mice expressing human AβPP containing the wt β-secretase site and the London mutant β-secretase site sequences are used. Delivering a drug by gavage offers the advantage of accurate dosing but is traumatic and thus only suitable for relatively short dosing periods (up to about a week). Delivery by gavage is used for the guinea pig studies. Aloxistatin is suspended in Me2SO at the indicated concentrations (0.1, 1.0, 5, and 10 mg/kg) and administered by gavage daily using a feeding tube. |
| Assay |
Cell proliferation and Apoptosis are assessed by staining for a proliferation marker, Ki67, or an apoptotic marker, cleaved Caspase 3. MCF10 variants are grown in 3D rBM overlay cultures for 4 days and are treated with 0.1 % DMSO, 5 μM CA074Me or 5 μM Aloxistatin. Structures are considered to be Caspase 3 positive if they contained at least one cell that is positive for cleaved Caspase 3 and the positive cell(s) is not localized in the center of a developing lumen. |
| Complexity |
450 |
| Exact Mass |
342.215485 |
| Index Of Refraction |
1.530 |
| In Vitro |
Aloxistatin (E64d) is a broad-spectrum cell-permeable inhibitor of cysteine proteases. Inhibition of protease-resistant prion protein (PrP-res) accumulation in ScNB cells by cysteine protease inhibitor Aloxistatin (E64d) with IC50 of 0.5±0.11 μM. It is able to completely block turnover of the CatL substrate Z-Phe-Arg-aminomethylcoumarin, when pre-incubated with NK-92 or YT 5 cells. |
| In Vivo |
Oral administration of Aloxistatin (E64d) to guinea pigs results in a dose-dependent reduction in brain, CSF and plasma Aβ(40) and Aβ(42). Aloxistatin also causes a biphasic dose-dependent reduction in brain CTFβ and a dose-dependent increase in brain sAβPPα. It inhibits the increases in the expression of AT1AR and ACE genes in rats. Administration of RNH-6270 or Aloxistatin reduces the increase in the superoxide production of the intramyocardial coronary arteries in HF rats. |
| PSA |
97.03000 |
| Target |
Cathepsin; SARS-CoV |
| Vapor Pressure |
0.0±2.6 mmHg at 25°C |
| XLogP3-AA |
2.3 |
![{PARAM:[Name]}()](https://resource.bocsci.com/structure/88321-09-9.gif)
