Aloxistatin

Category	SARS-CoV
CAS	88321-09-9
Description	Aloxistatin is an inhibitor of cathepsins B and L as well as a potential inhibitor of calpain, which predicted to function against SARS-CoV-2 infection.

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Product Information

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.
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