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E-64-c (Synonyms: Loxistatin Acid, NSC 694279)

Catalog No.GC16505

An active metabolite of E-64d

Products are for research use only. Not for human use. We do not sell to patients.

E-64-c Chemical Structure

Cas No.: 76684-89-4

Size Price Stock Qty
10mM (in 1mL DMSO)
$155.00
In stock
1mg
$34.00
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5mg
$138.00
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25mg
$547.00
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100mg
$1,385.00
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500mg
$3,976.00
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1g
$6,159.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

Neuronal chromaffin cells

Preparation method

The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.

Reacting condition

10 μM

Applications

In neuronal chromaffin cells, E-64-c inhibited the production of the 12 ~ 14 kDa β-secretase product from APP. In addition, when tested in isolated, intact secretory vesicles, E-64-c reduced the production of Aβ (1 ~ 40). These results indicated an important role of E-64-c in β-secretase processing of APP in neuronal chromaffin cells.

Animal experiment [2]:

Animal models

Rat models of cerebral ischemia

Dosage form

400 mg/kg; i.p.; b.i.d, for 3 days

Applications

In rat models of cerebral ischemia, E-64-c significantly inhibited the ischemia-induced depletion of microtubule-associated protein 2 (MAP2). E-64-c increased MAP2 levels to 55 ± 25.7% of control levels (sham-operated rats used as controls). However, E-64-c showed no marked effect on the decrease of myelin-associated glycoprotein caused by ischemia.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. Hook VY, Reisine TD. Cysteine proteases are the major beta-secretase in the regulated secretory pathway that provides most of the beta-amyloid in Alzheimer's disease: role of BACE 1 in the constitutive secretory pathway. J Neurosci Res. 2003 Nov 1;74(3):393-405.

[2]. 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.

Background

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.

Chemical Properties

Cas No. 76684-89-4 SDF
Synonyms Loxistatin Acid, NSC 694279
Chemical Name (2S,3S)-3-[[(2S)-4-methyl-1-(3-methylbutylamino)-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylic acid
Canonical SMILES CC(C)CCNC(=O)C(CC(C)C)NC(=O)C1C(O1)C(=O)O
Formula C15H26N2O5 M.Wt 314.4
Solubility ≥ 31.4mg/mL in DMSO, ≥ 111.8 mg/mL in EtOH Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 3.1807 mL 15.9033 mL 31.8066 mL
5 mM 0.6361 mL 3.1807 mL 6.3613 mL
10 mM 0.3181 mL 1.5903 mL 3.1807 mL
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