| Identification | Back Directory | [Name]
EST | [CAS]
88321-09-9 | [Synonyms]
EST
E-64D
ep453
Estate
CS-1622
NSC694281
oxistatin
E64d,E-64d
LOXASTATIN
LOXISTATIN
NSC-694281
NSC 694281
aloxistatin
Aloxistatin (E64d
E64c ethyl ester)
E64d, NSC-694281)
Aloxistatin(E-64d)
E-64-D(LOXISTATINE)
E 64d (Aloxistatin)
Aloxistatin (Loxistatin
E-64d [for Biochemical Research]
EST - CAS 88321-09-9 - Calbiochem
Aloxistatin (E-64d) EST Loxistatin
COT (30-397), active, GST tagged human
L-trans-Epoxysuccinyl(OEt)-Leu-3-methylbuty
(2S,3S)-trans-epoxysuccinyl-L-*leucylamido-3-meth
L-TRANS-EPOXYSUCCINYL(OET)-LEU-3-METHYLBUTYLAMIDE
ethylester,(2s-(2-alpha,3-beta(r*)))-mino)carbonyl)
trans-epoxysuccinyl-L-leucylamido 3-methylbutane ethyl
L-TRANS-EPOXYSUCCINYL-LEU-3-METHYLBUTYLAMIDE-ETHYL ESTER
E-64(Trans-Epoxysuccinyl-L-Leucylamido-(4-Guanidino)Butane)
(2S,3S)-ETHYL-TRANS-EPOXYSUCCINYL-L-LEUCYLAMIDO-3-METHYLBUTANE
(2S,3S)-TRANS-EPOXYSUCCINYL-L-LEUCYLAMIDO-3-METHYLBUTANE ETHYL ESTER
Aloxistatin, 98%, irreversible cell-permeable cysteine protease inhibitor
(2S,3S)-trans-Epoxysuccinyl-L-leucylaMido-3-Methylbutane ethyl ester, EST
(L-3TRANS-ETHOXYCARBONYLOXIRANE-2-CARBONYL)-L-LEUCINE-(3-METHYLBUTYL)AMIDE
EST, (2S,3S)-trans-Epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester
E-64d, L-trans-Epoxysuccinyl(OEt)-Leu-3-MethylbutylaMide, EP453, Aloxistatin, Loxistatin
ALOXISTATIN;E64D;E 64D;LOXISTATIN;E-64C ETHYL ESTER;EP 453;NSC 694281;NSC694281;NSC-694281
(2S,3S)-3-[[[(1S)-3-Methyl-1-[[(3-methylbutyl)amino]carbonyl]-butyl]amino]carbonyl]-2-oxiranec
(2S,3S)-ethyl 3-(((S)-1-(isopentylaMino)-4-Methyl-1-oxopentan-2-yl)carbaMoyl)oxirane-2-carboxylate
Ethyl (2S,3S)-3-[[(2S)-4-Methyl-1-[(3-methylbutyl)amino]-1-oxo-2-pentanyl]carbamoyl]-2-oxiranecarboxylate
[2S,3S,(+)]-3β-[(S)-3-Methyl-1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2α-oxiranecarboxylic acid ethyl ester
3-[[[(1S)-3-methyl-1[[(3S-methylbutyl)amino]carbonyl]butyl]amino]carbonyl]-2S-oxiranecarboxylic acid, ethyl ester
(2S,3S)-3-[[(2S)-4-Methyl-1-[(3-methylbutyl)amino]-1-oxo-2-pentanyl]carbamoyl]-2-oxiranecarboxylic Acid Ethyl Ester
(2S)-3β-[[[(S)-3-Methyl-1-[[(3-methylbutyl)amino]carbonyl]butyl]amino]carbonyl]oxirane-2α-carboxylic acid ethyl ester
(2S,3S)-3-[[[(1S)-3-Methyl-1-[[(3-Methylbutyl)aMino]carbonyl]butyl]aMino]carbonyl]-2-oxiranecarboxylic acid ethyl ester
2-Oxiranecarboxylicacid,3-[[[(1S)-3-methyl-1-[[(3-methylbutyl)amino]carbonyl]butyl]amino]carbonyl]-,ethyl ester, (2S,3S)- | [Molecular Formula]
C17H30N2O5 | [MDL Number]
MFCD00132883 | [MOL File]
88321-09-9.mol | [Molecular Weight]
342.43 |
| Chemical Properties | Back Directory | [Melting point ]
126.2°C | [Boiling point ]
477.88°C (rough estimate) | [density ]
1.0657 (rough estimate) | [refractive index ]
1.5800 (estimate) | [storage temp. ]
−20°C
| [solubility ]
Soluble in DMSO, DMF or ethanol | [form ]
White solid | [pka]
13.32±0.40(Predicted) | [color ]
Fine needles from EtOH | [biological source]
synthetic (organic) | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month. |
| Hazard Information | Back Directory | [Description]
E-64d is an irreversible, membrane-permeable inhibitor of lysosomal and cytosolic cysteine proteases and has diverse biological activities.1,2,3,4 It is a synthetic analog of E-64 (Item No. 10007963) and prodrug form of E-64c (Item No. 10007964) that inhibits calpain and the cysteine proteases cathepsins F, -K, -B, -H, and -L.1,5 E-64d (20-200 μM) induces cell cycle arrest at the G2/M phase in A431 human epidermoid carcinoma cells.2 It inhibits protease-resistant prion protein accumulation in scrapie-infected neuroblastoma cells with an IC50 value of 0.5 μM.3 E-46d also inhibits entry of vesicular stomatitis virus (VSV) particles pseudotyped with severe acute respiratory syndrome coronavirus (SARS-CoV) or SARS-CoV-2 spike glycoprotein into Vero cells, an effect that is reduced by expression of the serine protease TMPRSS2.4 | [Uses]
E-64d is an inhibitor of cathepsins B and L as well as a potential inhibitor of calpain. E-64d has been shown to inhibit lysosomal proteases. E-64d has been used in combination with Prepstatin A to in
terfere with autolysosomal digestion. E-64d displays neurovascular and neuronal protective effects after focal cerebral ischemia in rats. | [Definition]
ChEBI: An L-leucine derivative that is the amide obtained by formal condensation of the carboxy group of (2S,3S)-3-(ethoxycarbonyl)oxirane-2-carboxylic acid with the amino group of N-(3-methylb
tyl)-L-leucinamide. | [Biological Activity]
Cell-permeable, ethyl ester of E-64-c. The ester is hydrolyzed by intracellular esterases to produce E-64-c. Inhibits calpain and cathepsins B, H, and L. Inhibits degradation of autophagic cargo inside autophagolysosomes. | [Biochem/physiol Actions]
E-64d is an epoxysuccinyl peptide and an inhibitor of cysteine protease cathepsin B, calpains 1 and 2. E-64d by its cathepsin B protease inhibition functionality, may serve as a potential drug for treating traumatic brain injury (TBI) and Alzheimer′s disease (AD). It inhibits gametocyte surface antigen resulting in a decreased oocyst production in Plasmodium falciparum. | [Safety Profile]
Moderately toxic by intraperitoneal route. An experimental teratogen. Experimental reproductive effects. Mutation data reported. Whenheated to decomposition it emits toxic fumes of NOx. | [Synthesis]
General procedure for the synthesis of ethyl (2S,3S)-3-(((S)-1-(isopentylamino)-4-methyl-1-oxopentan-2-yl)carbamoyl)ethylene oxide-2-carboxylate from rel-(2R,3R)-3-(ethoxycarbonyl)oxirane-2-carboxylate and N1-isopentyl-L-leucinamide under nitrogen protection: under nitrogen protection (2S,3S)-3-((S)-3-(isopentylamino)-1-(isopentylamino)oxirane-2-carboxylic acid (25g, 0.16mol) and (S)-1-(isopentylamino)-1-(isopentylamino)-1-(isopentylamino)-1-(isopentylamino)-1-(isopentylamino)-1-(isopentylamino)-1-(isopentylamino)carbamoyl)ethylene oxide-2-carboxylic acid was prepared. -(ethoxycarbonyl)oxirane-2-carboxylic acid (25 g, 0.16 mol) and (S)-1-(isoamylamino)-2-amino-4-methyl-1-oxopentane hydrochloride (38 g, 0.16 mol) were dissolved in dichloromethane (750 mL) and cooled to 0 °C (ice water bath). Subsequently 2-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (65 g, 0.17 mol) and diisopropylethylamine (DIPEA, 56 mL, 0.31 mol) were added. The reaction mixture was stirred at 0 °C for 1 h. After removing the ice bath, the reaction mixture was continued to be stirred for 2 h at room temperature. Upon completion of the reaction, the reaction mixture was diluted with dichloromethane (750 mL), washed sequentially with saturated sodium bicarbonate solution (2 times) and saturated sodium chloride solution (1 time), the organic phase was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give a yellow viscous oily crude product. The crude product was purified by a silica gel column (60 mm × 300 mm), eluting with a gradient of 10% to 50% ethyl acetate in hexane solution. The combined eluents (2.5 L) were collected and concentrated under reduced pressure to give E64d (53 g, 100% yield) as a white solid. Recrystallization of E64d (36 g) in methyl tert-butyl ether in 1% ethanol (MTBE, 535 mL) afforded white short needle-like crystals of E64d (25 g, 69% yield) with a melting point of 123-124 °C.1H NMR (500 MHz, CDCl3) δ 6.68 (d, J=8.4 Hz, 1H), 6.08 (br s, 1H), 6.08 (br s, 1H), 6.08 (br s, 1H), 6.08 (br s, 1H), and 6.08 (br s, 1H). 4.36-4.40 (m, 1H), 4.21-4.28 (m, 2H), 3.67 (d, J=1.9 Hz, 1H), 3.46 (d, J=1.9 Hz, 1H), 3.19-3.30 (m, 2H), 1.49-1.65 (m, 4H), 1.38 (q, J=7.4 Hz, 2H), 1.30 (t, J= 7.0 Hz, 3H), 0.89-0.93 (m, 12H); ESI MS m/z 343.2 (M+H)+; elemental analysis (C17H30N2O5) is in accordance with the theoretical values; HPLC purity is in accordance with the requirements. | [storage]
Store at -20°C | [References]
1) McGowan?et al.?(1989),?Inhibition of calpain in intact platelets by the thiol protease inhibitor E-64d; Biochem. Biophys. Res. Commun.,?158?432
2) Wilcox and Mason (1992),?Inhibition of cysteine proteinases in lysosomes and whole cells; Biochem. J.,?285?495
3) Mizushima?et al.?(2010), Methods in mammalian autophagy research; Cell,?140?313 |
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