E-64-cInhibitor of cysteine proteinases CAS# 76684-89-4 |
2D Structure
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Quality Control & MSDS
3D structure
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Cas No. | 76684-89-4 | SDF | Download SDF |
PubChem ID | 123664 | Appearance | Powder |
Formula | C15H26N2O5 | M.Wt | 314.4 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : 250 mg/mL (795.22 mM; Need ultrasonic) | ||
Chemical Name | (2S,3S)-3-[[(2S)-4-methyl-1-(3-methylbutylamino)-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylic acid | ||
SMILES | CC(C)CCNC(=O)C(CC(C)C)NC(=O)C1C(O1)C(=O)O | ||
Standard InChIKey | SCMSYZJDIQPSDI-SRVKXCTJSA-N | ||
Standard InChI | InChI=1S/C15H26N2O5/c1-8(2)5-6-16-13(18)10(7-9(3)4)17-14(19)11-12(22-11)15(20)21/h8-12H,5-7H2,1-4H3,(H,16,18)(H,17,19)(H,20,21)/t10-,11-,12-/m0/s1 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | E-64-c is an effective synthetic calpain inhibitor composed from E-64, which also inhibits cathepsin B, cathepsin H, and cathepsin L (cysteine proteases). | |||||
Targets | cathepsins B | cathepsins H | cathepsins L |
E-64-c Dilution Calculator
E-64-c Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 3.1807 mL | 15.9033 mL | 31.8066 mL | 63.6132 mL | 79.5165 mL |
5 mM | 0.6361 mL | 3.1807 mL | 6.3613 mL | 12.7226 mL | 15.9033 mL |
10 mM | 0.3181 mL | 1.5903 mL | 3.1807 mL | 6.3613 mL | 7.9517 mL |
50 mM | 0.0636 mL | 0.3181 mL | 0.6361 mL | 1.2723 mL | 1.5903 mL |
100 mM | 0.0318 mL | 0.159 mL | 0.3181 mL | 0.6361 mL | 0.7952 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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E-64-c, which is also known as Ep-475, is an analog of E-64 and inhibitor of cysteine proteinases. [1]
The cysteine proteinases, of which Cathepsins B and H and cathepsin L exist in mammals, contain an essential highly reactive thiol group, and therefore are inhibited by thiol-blocking reagents such as iodoacetate and mercuribenzoate. E-64-c showed promise of acting as class-specific inhibitors for the cysteine proteinases. X-ray diffraction shows that E-64-c binds to papain through a thioether covalent bond.[1]
E-64-c, which is an analog of E-64, has proved to be substantially more reactive than E-64 with cathepsins B and L. Cathepsins B and H from human liver and rat cathepsin L were used to measure the rate constants of inhibition of E-64-c, which indicated the rate constants of inactivation of cathepsins B, H and L were 298000, 2018, 206000 M-1 s-1 , respectively[2].
E-64-c was injected subcutaneously, in various doses, daily for 80 days into dystrophic chickens, the activities of cathepsin B and cathepsin H were reduced to the levels in control chickens. E-64-c showed dose-dependent activities on inhibiting cathepsin H and B. However, cathepsin D is not sensitive to E-64-c. Moreover, 10 mg/kg per 8 h of an oil emulsion of E-64-c injection reduced protein degradation 20% in muscles from burned rats. E-64c, which also inhibits calpain , was administered at a dose of 400 mg/kg twice a day for 3 days to middle cerebral artery occlusion mice. The MAP2 levels was increased compared to control and the depletion was significantly inhibited.[3,4]
References:
1.Yamamoto D, Matsumoto K, Ohishi H, et al. Refined x-ray structure of papain. E-64-c complex at 2.1-A resolution[J]. Journal of Biological Chemistry, 1991, 266(22): 14771-14777.
2.Barrett A J, Kembhavi A A, Brown M A, et al. L-trans-Epoxysuccinyl-leucylamido (4-guanidino) butane (E-64) and its analogues as inhibitors of cysteine proteinases including cathepsins B, H and L[J]. Biochem. J, 1982, 201: 189-198.
3.Clark A S, Kelly R A, Mitch W E. Systemic response to thermal injury in rats. Accelerated protein degradation and altered glucose utilization in muscle[J]. Journal of Clinical Investigation, 1984, 74(3): 888.
4.Inuzuka T, Tamura A, Sato S, et al. Suppressive effect of E-64c on ischemic degradation of cerebral proteins following occlusion of the middle cerebral artery in rats[J]. Brain research, 1990, 526(1): 177-179.
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Refined x-ray structure of papain.E-64-c complex at 2.1-A resolution.[Pubmed:1860874]
J Biol Chem. 1991 Aug 5;266(22):14771-7.
E-64-c, a synthetic cysteine protease inhibitor designed from E-64, binds to papain through a thioether covalent bond. The x-ray diffraction data for 2.1-A resolution were used to determine the three-dimensional structure of this complex and refined it to R = 0.159. 0.159. In the complex structure, the configurational conversion from S to R took place on the epoxy carbon of E-64-c, implying that the nucleophilic attack of the Cys-25 thiol group occurs at the opposite side of the epoxy oxygen atom. The leucyl and isoamylamide groups of E-64-c were strongly fixed to papain S subsites by specific interactions, including hydrogen bonding to the Gly-66 residue. The carboxyl-terminal anion of E-64-c formed an electrostatic interaction with the protonated His-159 imidazole ring (O-...HN+ = 3.76 A) and consequently prevented the participation of this residue in the hydrolytic charge-relay system. No significant distortion caused by the binding of E-64-c was shown in the secondary structure of papain. It is important to note that inhibitor and substrate have opposite binding modes for the peptide groups. The possible relationship between the binding mode and inhibitory activity is discussed on the basis of the crystal structure of this complex.
Mode of binding of E-64-c, a potent thiol protease inhibitor, to papain as determined by X-ray crystal analysis of the complex.[Pubmed:2924921]
FEBS Lett. 1989 Mar 13;245(1-2):177-80.
The three-dimensional structure of the E-64-c-papain complex has been determined by X-ray crystal analysis at 2.5 A resolution (conventional R = 26.9%). The structure determined indicates that: (i) the C2 atom of the oxirane ring of E-64-c is covalently bound by the S gamma atom of Cys-25 of papain; (ii) this covalent bond formation results in a configurational conversion of the oxirane C2 atom from the S- to the R-form; and (iii) extensive hydrogen bonding and hydrophobic interactions are responsible for the specific interaction of the E-64-c molecule with papain.
The effect of an in vivo-injected thiol protease inhibitor, E-64-c, on the calcium-induced degeneration of myofilaments.[Pubmed:6279581]
J Biochem. 1981 Nov;90(5):1557-60.
The role of intracellular calcium-dependent proteinase(s) has been investigated in intact rat muscle. When calcium ions were introduced into intact muscle in vitro with ionophore A23187, Z-line loss and concomitant release of alpha-actinin into the medium were observed. The calcium-induced release of alpha-actinin was not diminished in the muscle with in vivo-injection of a thiol protease inhibitor, E-64-c. Intramuscular concentrations of E-64-c were also measured after pulse labeling with [3H]E-64-c followed by subcellular fractionation. Most of the inhibitor was localized in the cytosol, not in the lysosome. Therefore, we conclude that cytosolic as well as lysosomal proteinases in muscle are not inhibited by the in vivo labeling of the protease inhibitor (10 mg/kg).
The importance of Val-157 hydrophobic interaction for papain inhibitory activity of an epoxysuccinyl amino acid derivative. A structure-activity relationship based on the crystal structure of the papain-E-64-c complex.[Pubmed:2332044]
FEBS Lett. 1990 Apr 9;263(1):134-6.
Based on the crystal structure of the papain-E-64-c complex, 3-dimensional binding modes of a series of epoxysuccinyl amino acid derivatives to the papain active site have been constructed and the structure-inhibitory activity relationship has been analyzed using the accessible surface area and nonbonded energy parameters. The result indicates the importance of the hydrophobic interaction between the amino acid side chain of the inhibitor and the papain Val-157 residue for revealing the potent inhibitory activity.