66701-25-5

Basic information

• Product Name: (L-3-TRANS-CARBOXYOXIRANE-2-CARBONYL)-L-LEUCYLAGMATINE HEMIHYDRATE
• Synonyms: (2S, 3S)-TRANS-EPOXY SUCCINYL-L-LEUCYLAMIDO-(4-GUANIDINO) BUTANE;L-TRANS-3-CARBOXYOXIRAN-2-CARBONYL-L-LEUCYLAGMATINE;L-TRANS-EPOXYSUCCINYL-LEU-4-GUANIDINOBUTYLAMIDE;L-TRANS-EPOXYSUCCINYL-LEU-AGMATINE;L-TRANS-EPOXYSUCCINYL-LEUCYLAMIDE-(4-GUANIDO)-BUTANE;EPOXYSUCCINYL-L-LEUCYLAMIDO-(4-GUANIDINO)BUTANE;E-64 HEMIHYDRATE;E-64 PROTEASE INHIBITOR
• CAS NO: 66701-25-5
• Molecular Formula: C₁₅H₂₇N₅O₅
• Molecular Weight: 357.41
• EINECS: 613-978-4
• Product Categories: Inhibitors;Pepetides;ProteaseInhibitors;peptides;inhibitor
• Mol File: 66701-25-5.mol
• Article Data: 0

Chemical Properties

• Appearance: white solid
• Density: 1.446 g/cm³
• Refractive Index: 1.617
• Storage Temp.: 2-8°C
• Solubility: H2O: 20 mg/mL, clear, colorless
• PKA: 3.16±0.40(Predicted)
• Water Solubility: Soluble in DMSO (25mg/ml), or water (20mg/ml)
• Sensitive: Light Sensitive
• Stability: Stable for 1 year from date of purchase as supplied.
• BRN: 1405664
• CAS DataBase Reference: (L-3-TRANS-CARBOXYOXIRANE-2-CARBONYL)-L-LEUCYLAGMATINE HEMIHYDRATE(CAS DataBase Reference)
• NIST Chemistry Reference: (L-3-TRANS-CARBOXYOXIRANE-2-CARBONYL)-L-LEUCYLAGMATINE HEMIHYDRATE(66701-25-5)
• EPA Substance Registry System: (L-3-TRANS-CARBOXYOXIRANE-2-CARBONYL)-L-LEUCYLAGMATINE HEMIHYDRATE(66701-25-5)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• RTECS: RR0390000
• F: 10
• Hazardous Substances Data: 66701-25-5(Hazardous Substances Data)

Usage

Description

(L-3-TRANS-CARBOXYOXIRANE-2-CARBONYL)-L-LEUCYLAGMATINE HEMIHYDRATE, also known as E-64, is a cell-permeable, epoxysuccinyl peptide irreversible inhibitor derived from the mold Aspergillus japonicus TPR-64. It is recognized for its ability to inhibit various cysteine proteases, including cathepsin K, L, and S, as well as other enzymes such as calpain, cathepsin B, and H, and papain. E-64 has a molecular formula of C20H33N5O6 and is effective in blocking the breakdown of methaemoglobin and the oxidation of oxyhaemoglobin by InpA. It also plays a role in studying excystation in Giardia lamblia.

Uses

Used in Pharmaceutical Applications:
(L-3-TRANS-CARBOXYOXIRANE-2-CARBONYL)-L-LEUCYLAGMATINE HEMIHYDRATE is used as a broad-spectrum cysteine proteinase and calpain activation inhibitor for its ability to effectively inhibit various cysteine proteases, making it a valuable compound in the development of therapeutic agents targeting protease-related diseases.
Used in Research Applications:
In the field of research, (L-3-TRANS-CARBOXYOXIRANE-2-CARBONYL)-L-LEUCYLAGMATINE HEMIHYDRATE is used as an effective ligand for affinity purification of cysteine proteases. When coupled to a thiolated affinity matrix, it retains its specificity while allowing for reversible binding, which is crucial for studying the interactions and functions of these proteases.
Used in Pathology Studies:
(L-3-TRANS-CARBOXYOXIRANE-2-CARBONYL)-L-LEUCYLAGMATINE HEMIHYDRATE is used as a research tool to investigate the calpain-dependent apoptosis pathway in T cells and its role in heat-induced apoptosis in FM3A cells. This helps in understanding the mechanisms of cell death and the potential therapeutic applications of E-64 in treating diseases associated with apoptosis.
Used in Microbiology:
In the field of microbiology, (L-3-TRANS-CARBOXYOXIRANE-2-CARBONYL)-L-LEUCYLAGMATINE HEMIHYDRATE is used to study the breakdown of methaemoglobin and the oxidation of oxyhaemoglobin by InpA in Prevotella intermediate, providing insights into the bacterial metabolism and its interaction with host cells.
Used in Parasitology:
(L-3-TRANS-CARBOXYOXIRANE-2-CARBONYL)-L-LEUCYLAGMATINE HEMIHYDRATE is used in the study of excystation in Giardia lamblia, a parasitic protozoan that causes giardiasis. Understanding the process of excystation is essential for developing strategies to combat parasitic infections.

Hazard

A reproductive hazard.

Biochem/physiol Actions

E-64 is an irreversible, potent, and highly selective cysteine protease inhibitor. E-64 does not react with the functional thiol group of non-protease enzymes, such as L-lactate dehydrogenase or creatine kinase. E-64 will not inhibit serine proteases (except trypsin) like other cysteine protease inhibitors, leupeptin and antipain. The trans-epoxysuccinyl group (active moiety) of E-64 irreversibly binds to an active thiol group in many cysteine proteases, such as papain, actinidase, and cathepsins B, H, and L to form a thioether linkage. E-64 is a very useful cysteine protease inhibitor for use in in vivo studies because it has a specific inhibition, it is permeable in cells and tissues and has low toxicity.

References

1) Wang and Yuen (1994),?Calpain inhibition: an overview of its therapeutic potential; Trends Pharmacol. Sci.,?15?412 2) Barrett?et al.?(1982),?L-trans-Epoxysuccinyl-leucylamido(4-guanidino)butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H, and L; Biochem. J.,?201?189 3) Sarin?et al.?(1994),?Inhibition of activation-induced programmed cell death and restoration of defective immune responses of HIV+ donors by cysteine protease inhibitors; J. Immunol.,?153?862 4) Zhu?et al.?(1996),?Promotion of heat-induced apoptosis in FM3A cells by protease inhibitors; Biochem. Biophys. Res. Commun.,?225?924

InChI:InChI=1/C15H27N5O5/c1-8(2)7-9(20-13(22)10-11(25-10)14(23)24)12(21)18-5-3-4-6-19-15(16)17/h8-11H,3-7H2,1-2H3,(H,18,21)(H,20,22)(H,23,24)(H4,16,17,19)/t9-,10+,11+/m0/s1