E-64-D

BML-PI107

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Calpain and cathepsin inhibitor

Potent inhibitor of calpain and cathepsins
Used in autophagy research
highly cited

E-64-D is a cell-permeable ethyl ester of E-64-C (Prod. No. BML-PI106). The ester is hydrolyzed by intracellular esterases to produce E-64-C that inhibits calpain and cathepsins B, F, H, K, and L. E-64-D inhibits degradation of autophagic cargo inside autophagolysosomes, especially when used in combination with pepstatin (Prod. No. ALX-260-085). E-64-D combined with camostat mesylate also inhibits entry of SARS-CoV-2 in cells in vitro.

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Product Details

Alternative Name	2S,3S-trans-(Ethoxycarbonyloxirane-2-carbonyl)-L-leucine-(3-methylbutyl) amide, Aloxistatin
Appearance	White solid.
CAS	88321-09-9
Couple Target	Calpain, Cathepsin, Protease
Couple Type	Inhibitor
Formula	C₁₇H₃₀N₂O₅
Identity	Identity determined by MS.
MW	342.4
Purity	≥98% (HPLC)
Solubility	Soluble in DMSO (20mg/ml) or 100% ethanol (>10mg/ml).
Source	Synthetic.

Handling & Storage

Use/Stability	As indicated on product label or CoA when stored as recommended. Store, as supplied, at -20°C for up to 1 year. Store solutions at -20°C for up to 2 months.
Long Term Storage	-20°C
Shipping	Ambient Temperature

Regulatory Status	RUO – Research Use Only

Hepatic lipid remodeling in cold exposure uncovers direct regulation of bis(monoacylglycero)phosphate lipids by phospholipase A2 group XV: J.W. Davidson, et al.; Cell Metab. 37, 1413 (2025), Abstract
Cellular depletion of major cathepsin proteases reveals their concerted activities for lysosomal proteolysis: L. Gallwitz, et al.; Cell. Mol. Life Sci. 22, 227 (2024), Abstract
Neuronal autosis is Na+/K+-ATPase alpha 3-dependent and involved in hypoxic-ischemic neuronal death: Depierre, P., Ginet, V., et al.; Cell Death Dis. 15, 363 (2024), Abstract
Dynamic association of the intramembrane proteases SPPL2a/b and their substrates with tetraspanin-enriched microdomains: Leinung, N., Mentrup, T., et al.; iScience 26, 107819 (2023), Abstract
LAMP3 inhibits autophagy and contributes to cell death by lysosomal membrane permeabilization: T. Tanaka, et al.; Autophagy 18, 1629 (2022), Abstract — Full Text
Lysosomal ceramides regulate cathepsin B-mediated processing of saposin C and glucocerebrosidase activity: M.J. Kim, et al.; Hum. Mol. Genet. 31, 2424 (2022), Abstract
SerpinB3 drives cancer stem cell survival in glioblastoma: A. Lauko, et al.; Cell Rep. 40, 111348 (2022), Abstract — Full Text
The spike-stabilizing D614G mutation interacts with S1/S2 cleavage site mutations to promote the infectious potential of SARS-CoV-2 variants: S. Gellenoncourt, et al.; J. Virol. 96, e0130122 (2022), Abstract — Full Text
Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis: T. Mentrup, et al.; Nat. Commun. 13, 1880 (2022), Abstract
Lysosomal degradation ensures accurate chromosomal segregation to prevent chromosomal instability: Almacellas, E., Pelletier, J., et al.; Autophagy 17, 796 (2021), Abstract