Aloxistatin | E-64d | CAS#88321-09-9 | calpain and autophagy inhibitor

MedKoo Cat#: 319511 | Name: Aloxistatin (E-64d)

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Aloxistatin (E-64d), is a selective cysteine protease inhibitor or calpain and autophagy inhibitor. E-64d prevents in vitro cerulein- induced trypsinogen activation. E-64d can enter the intact cell and inhibit calpain. E-64d has been shown safe for the treatment of Alzheimer's disease in human. E-64d is potentially useful in the treatment of developmental seizure-induced brain damage both by regulating abnormal zinc signal transduction and through the modulation of altered lipid metabolism via ApoE/clusterin pathway in hippocampus.

Chemical Structure

Aloxistatin (E-64d)

CAS#88321-09-9

Theoretical Analysis

MedKoo Cat#: 319511

Name: Aloxistatin (E-64d)

CAS#: 88321-09-9

Chemical Formula: C17H30N2O5

Exact Mass: 342.2155

Molecular Weight: 342.44

Elemental Analysis: C, 59.63; H, 8.83; N, 8.18; O, 23.36

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship

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Related CAS #

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Synonym

E-64d; E 64d; E64d; E64-d; E64-d; E64 d; ethyl ester Loxistatin; NSC 694281; NSC694281; NSC-694281; EST; EP-453; EP453; EP 453; Aloxistatin

IUPAC/Chemical Name

ethyl (2S,3S)-3-(((S)-1-(isopentylamino)-4-methyl-1-oxopentan-2-yl)carbamoyl)oxirane-2-carboxylate

InChi Key

SRVFFFJZQVENJC-IHRRRGAJSA-N

InChi Code

InChI=1S/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

SMILES Code

CCOC([C@@H]1[C@@H](C(N[C@H](C(NCCC(C)C)=O)CC(C)C)=O)O1)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#C9R07B09

QC Data

View QC data: current batch, Lot#C9R07B09

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Aloxistatin (E64d) is a cell-permeable and irreversible broad-spectrum cysteine protease inhibitor. Aloxistatin (E64d) exhibits entry-blocking effect for MERS-CoV.

In vitro activity:

E-64d, a membrane permeant derivative of E-64c, a thiol protease inhibitor (Tamai et al. (1986) J. Pharmacobio-Dyn. 9, 672-677), was tested for ability to inhibit calpain activity in intact platelets. Calpain activity was measured by proteolysis of actin-binding protein and talin, two known substrates of calpain. Incubation of platelets with E-64c (not permeant) or E-64d before lysis prevented proteolysis after lysis. When the platelets were incubated with E-64c or E-64d and then washed to remove the drugs before lysis, only E-64d inhibited proteolysis. When platelets were incubated with E-64c or E-64d and then activated with A23187 plus calcium, a treatment that activates intraplatelet calpain, only E-64d inhibited proteolysis. These results indicate that E-64d can enter the intact cell and inhibit calpain. Reference: Biochem Biophys Res Commun. 1989 Jan 31;158(2):432-5. https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(89)80065-8

In vivo activity:

To evaluate that issue, a cysteine protease inhibitor, E64d, was orally administered to normal guinea pigs or transgenic mice expressing human AβPP, both of which express the human wild-type β-secretase site sequence. In guinea pigs, oral E64d administration caused a dose-dependent reduction of up to 92% in brain, CSF, and plasma of Aβ40 and Aβ42, a reduction of up to 50% in the C-terminal β-secretase fragment (CTFβ), and a 91% reduction in brain cathepsin B activity, but increased brain BACE1 activity by 20%. In transgenic AD mice, oral E64d administration improved memory deficits and reduced brain Aβ40 and Aβ42, amyloid plaque, brain CTFβ, and brain cathepsin B activity, but increased brain BACE1 activity. It’s concluded that E64d likely reduces brain Aβ by inhibiting cathepsin B and not BACE1 β-secretase activity and that E64d therefore may have potential for treating AD patients. Reference: J Alzheimers Dis. 2011;26(2):387-408. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21613740/

	Solvent	mg/mL	mM
Solubility
	DMSO	50.0	146.02
	Ethanol	33.3	97.33

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 342.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. McGowan EB, Becker E, Detwiler TC. Inhibition of calpain in intact platelets by the thiol protease inhibitor E-64d. Biochem Biophys Res Commun. 1989 Jan 31;158(2):432-5. doi: 10.1016/s0006-291x(89)80065-8. PMID: 2537073.

In vivo protocol:

1. Hook G, Hook V, Kindy M. The cysteine protease inhibitor, E64d, reduces brain amyloid-β and improves memory deficits in Alzheimer's disease animal models by inhibiting cathepsin B, but not BACE1, β-secretase activity. J Alzheimers Dis. 2011;26(2):387-408. doi: 10.3233/JAD-2011-110101. PMID: 21613740; PMCID: PMC4317342. 2. Cheng XW, Murohara T, Kuzuya M, Izawa H, Sasaki T, Obata K, Nagata K, Nishizawa T, Kobayashi M, Yamada T, Kim W, Sato K, Shi GP, Okumura K, Yokota M. Superoxide-dependent cathepsin activation is associated with hypertensive myocardial remodeling and represents a target for angiotensin II type 1 receptor blocker treatment. Am J Pathol. 2008 Aug;173(2):358-69. doi: 10.2353/ajpath.2008.071126. Epub 2008 Jun 26. PMID: 18583318; PMCID: PMC2475774.

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