88321-09-9 Usage
Description
Aloxistatin is a synthetic inhibitor that targets lysosomal and cytosolic cysteine proteases, including cathepsins B and L, as well as calpain. It is an analog of E-64 and a prodrug form of E-64c, exhibiting diverse biological activities. Aloxistatin is used in various applications across different industries due to its ability to modulate protease activity and provide protective effects.
Used in Pharmaceutical Industry:
Aloxistatin is used as a lysosomal inhibitor for human acute promyelocytic leukemia NB4 cells and Huh-7 cells, playing a crucial role in cancer research and treatment development.
Aloxistatin is used as a protease inhibitor in free calcium physiological tyrode solution for perfusion into isolated heart samples, contributing to cardiovascular research and potential therapeutic applications.
Used in Neuroprotection:
Aloxistatin is used in combination with Prepstatin A to interfere with autolysosomal digestion, highlighting its potential in neurodegenerative disease research and treatment.
Aloxistatin displays neurovascular and neuronal protective effects after focal cerebral ischemia in rats, indicating its potential use in stroke treatment and neuroprotection.
Used in Virology:
Aloxistatin inhibits the entry of vesicular stomatitis virus (VSV) particles pseudotyped with severe acute respiratory syndrome coronavirus (SARS-CoV) or SARS-CoV-2 spike glycoprotein into Vero cells, an effect that is reduced by expression of the serine protease TMPRSS2. This suggests its potential use in antiviral research and the development of treatments for viral infections.
Biochem/physiol Actions
E-64d is an epoxysuccinyl peptide and an inhibitor of cysteine protease cathepsin B, calpains 1 and 2. E-64d by its cathepsin B protease inhibition functionality, may serve as a potential drug for treating traumatic brain injury (TBI) and Alzheimer′s disease (AD). It inhibits gametocyte surface antigen resulting in a decreased oocyst production in Plasmodium falciparum.
Safety Profile
Moderately toxic by intraperitoneal route. An experimental teratogen. Experimental reproductive effects. Mutation data reported. Whenheated to decomposition it emits toxic fumes of NOx.
References
1) McGowan?et al.?(1989),?Inhibition of calpain in intact platelets by the thiol protease inhibitor E-64d; Biochem. Biophys. Res. Commun.,?158?432
2) Wilcox and Mason (1992),?Inhibition of cysteine proteinases in lysosomes and whole cells; Biochem. J.,?285?495
3) Mizushima?et al.?(2010), Methods in mammalian autophagy research; Cell,?140?313
Check Digit Verification of cas no
The CAS Registry Mumber 88321-09-9 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,8,3,2 and 1 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 88321-09:
(7*8)+(6*8)+(5*3)+(4*2)+(3*1)+(2*0)+(1*9)=139
139 % 10 = 9
So 88321-09-9 is a valid CAS Registry Number.
InChI:InChI=1/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
88321-09-9Relevant articles and documents
COMPOSITIONS AND METHODS FOR SYNTHESIZING (2S,3S)-TRANS-EPOXYSUCCINYL-L-LEUCYL-AMIDO-3-METHYLBUTANE ETHYL ESTER
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Paragraph 0056; 0059; 0063; 0070; 0071; 0110; 0113, (2017/07/06)
In alternative embodiments the invention provides methods for synthesizing AB-007 (also called loxistatin, E64d, EST or ((2S,3S)-trans-epoxysuccinyl-L-leucyl-amido-3-methylbutane ethyl ester) and its acid form E64c (loxistatin acid), and various synthetic
Stereoselective synthesis of the epoxysuccinyl peptide E-64c
Lygo, Barry,Gardiner, Stuart D.,To, Daniel C. M.
, p. 2063 - 2066 (2008/02/05)
A highly diastereoselective PTC epoxidation is employed in the synthesis of the potent cysteine protease inhibitor E-64c. Georg Thieme Verlag Stuttgart.
Mechanistic studies on the inactivation of papain by epoxysuccinyl inhibitors
Meara, Joseph P.,Rich, Daniel H.
, p. 3357 - 3366 (2007/10/03)
Analogs of the epoxysuccinyl peptide cysteine proteinase inhibitor, EP- 475 (2a), in which the free carboxylate has been replaced by hydroxamic acid, amide, methyl ketone, hydroxyl, and ethyl ester functionalities, have been synthesized. Individual rate c