88321-09-9

Basic information

• Product Name: EST
• Synonyms: (2S,3S)-3-[[[(1S)-3-Methyl-1-[[(3-Methylbutyl)aMino]carbonyl]butyl]aMino]carbonyl]-2-oxiranecarboxylic acid ethyl ester;(2S,3S)-trans-Epoxysuccinyl-L-leucylaMido-3-Methylbutane ethyl ester, EST;(2S,3S)-ethyl 3-(((S)-1-(isopentylaMino)-4-Methyl-1-oxopentan-2-yl)carbaMoyl)oxirane-2-carboxylate;Estate;oxistatin;E64d,E-64d;3-[[[(1S)-3-methyl-1[[(3S-methylbutyl)amino]carbonyl]butyl]amino]carbonyl]-2S-oxiranecarboxylic acid, ethyl ester;COT (30-397), active, GST tagged human
• CAS NO: 88321-09-9
• Molecular Formula: C17H30N2O5
• Molecular Weight: 342.43
• Product Categories: Inhibitors;peptides;Pepetides;ProteaseInhibitors
• Mol File: 88321-09-9.mol
• Article Data: 6

Chemical Properties

• Melting Point: 126.2°C
• Boiling Point: 477.88°C (rough estimate)
• Flash Point: 279.2°C
• Appearance: /
• Density: 1.0657 (rough estimate)
• Vapor Pressure: 1.2E-11mmHg at 25°C
• Refractive Index: 1.5800 (estimate)
• Storage Temp.: −20°C
• Solubility: Soluble in DMSO, DMF or ethanol
• 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.
• CAS DataBase Reference: EST(CAS DataBase Reference)
• NIST Chemistry Reference: EST(88321-09-9)
• EPA Substance Registry System: EST(88321-09-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36-24/25
• RIDADR: 3077
• WGK Germany: 2
• RTECS: RR0404300
• Hazardous Substances Data: 88321-09-9(Hazardous Substances Data)

Usage

Description

E-64d is an irreversible, membrane-permeable inhibitor of lysosomal and cytosolic cysteine proteases and has diverse biological activities. It is a synthetic analog of E-64 and prodrug form of E-64c that inhibits calpain and the cysteine proteases cathepsins F, -K, -B, -H, and -L. E-64d (20-200 μM) induces cell cycle arrest at the G2/M phase in A431 human epidermoid carcinoma cells. It inhibits protease-resistant prion protein accumulation in scrapie-infected neuroblastoma cells with an IC50 value of 0.5 μM. 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.

Uses

Different sources of media describe the Uses of 88321-09-9 differently. You can refer to the following data:
1. E-64d has been used as a lysosomal inhibitor in human acute promyelocytic leukemia NB4 cells and Huh-7?cells. It has also been used as a protease inhibitor in free calcium physiological tyrode solution for perfusion into the isolated heart samples.
2. 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.
3. 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 interfere 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.

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.

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

InChI:InChI=1/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

Upstream product

• 3291-46-1 (2S,3S)-diethyl oxirane-2,3-dicarboxylate 
• 107-85-7 1-amino-3-methylbutane 
• 63734-73-6 ethyl (2S,3S)-2,3-epoxysuccinate 
• 84851-37-6 (S)-1-(isopentylamino)-2-amino-4-methyl-1-oxopentan hydrochloride 
• 84851-37-6 N¹-isoamylleucinamide 
• 84863-67-2 (S)-t-butyl 1-(isopentylamino)-4-methyl-1-oxopentan-2-ylcarbamate 
• 66866-44-2 Boc-Leu-O-COO-isoBu 
• 13139-15-6 N-tert-butoxycarbonyl-L-leucine 
• 75657-73-7 N-((2S,3S)-3-trans-ethoxycarbonyloxiran-2-carbonyl)-L-leucine benzyl ester 
• 1738-77-8 L-leucine benzyl ester p-toluenesulfonate 
• 915697-62-0 C₂₁H₃₀N₂O₅ 
• 64-17-5 ethanol 
• 174759-66-1 N-[(2S,3S)-3-trans-ethoxycarbonyloxirane-2-carbonyl]-L-leucine 
• 100464-19-5 2-ethyl 3-(4-nitrophenyl) (2S,3S)-oxirane-2,3-dicarboxylate 

Downstream Products

• 179082-53-2 (2S,3S)-Oxirane-2,3-dicarboxylic acid 2-(benzyloxy-amide) 3-{[(S)-3-methyl-1-(3-methyl-butylcarbamoyl)-butyl]-amide} 
• 140660-53-3 (2S,3S)-3-[(S)-3-Methyl-1-(3-methyl-butylcarbamoyl)-butylcarbamoyl]-oxirane-2-carboxylic acid (S)-2-((S)-2-benzyloxycarbonylamino-4-methyl-pentanoylamino)-hexyl ester 
• 140660-55-5 5-<3-<2-ethyl>-1H-indolyl> (+)-(2S,3S)-3-<<(S)-3-methyl-1-<(3-methylbutyl)carbamoyl>butyl>carbamoyl>-2-oxiranecarboxylate 
• 140660-60-2 N-<2-<5-(benzyloxy)-1H-indol-3-yl>ethyl> (2S,3S)-3-<<(S)-3-methyl-1-<(3-methylbutyl)carbamoyl>butyl>carbamoyl>-2-oxiranecarboxamide 
• 140660-56-6 (R)-2-({(2S,3S)-3-[(S)-3-Methyl-1-(3-methyl-butylcarbamoyl)-butylcarbamoyl]-oxiranecarbonyl}-amino)-3-phenyl-propionic acid methyl ester 
• 140660-52-2 (2S,3S)-3-[(S)-3-Methyl-1-(3-methyl-butylcarbamoyl)-butylcarbamoyl]-oxirane-2-carboxylic acid 2-chloro-benzyl ester 
• 76684-89-4 loxistatin acid 

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Relevant articles and documents

COMPOSITIONS AND METHODS FOR SYNTHESIZING (2S,3S)-TRANS-EPOXYSUCCINYL-L-LEUCYL-AMIDO-3-METHYLBUTANE ETHYL ESTER

In alternative embodiments the invention provides methods for synthesizing AB-007 (also called loxistatin, E64d, EST or ((2S,3S)-trans-epoxysuccinyl-L-leucyl-amido-3-methylbutane ethyl ester) and its acid form E64c (loxistatin acid), and various synthetic

Stereoselective synthesis of the epoxysuccinyl peptide E-64c

A highly diastereoselective PTC epoxidation is employed in the synthesis of the potent cysteine protease inhibitor E-64c. Georg Thieme Verlag Stuttgart.

Mechanistic studies on the inactivation of papain by epoxysuccinyl inhibitors

Analogs of the epoxysuccinyl peptide cysteine proteinase inhibitor, EP- 475 (2a), in which the free carboxylate has been replaced by hydroxamic acid, amide, methyl ketone, hydroxyl, and ethyl ester functionalities, have been synthesized. Individual rate c