Chemistry:Aloxistatin
{{Drugbox | IUPAC_name = ethyl (2S,3S)-3-[[(2S)-4-methyl-1-(3-methylbutylamino)-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylate | image = Aloxistatin.svg | tradename = | legal_US = Investigational drug | legal_status =
| bioavailability = | metabolism = | elimination_half-life = | excretion =
| ATC_prefix = none | CAS_number = 88321-09-9 | PubChem = 65663 | UNII = L5W337AOUR | ChemSpiderID = 59098 | ChEMBL = 63440 | ChEBI = 101381
| C=17 | H=30 | N=2 | O=5 | SMILES = CCOC(=O)[C@@H]1[C@H](O1)C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C | StdInChI=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 | StdInChIKey = SRVFFFJZQVENJC-IHRRRGAJSA-N
Aloxistatin (loxistatin, E-64d, EST) is a drug which acts as a cysteine protease inhibitor and has anticoagulant effects. It is a synthetic analogue of E-64, a natural product derived from fungi.[1][2][3] It was researched for the treatment of muscular dystrophy but was not successful in human clinical trials,[4] though it has continued to be investigated for treatment of spinal cord injury, stroke and Alzheimer's disease.[5][6][7][8][9] It also shows antiviral effects.[10][11]
References
- ↑ "In vitro and in vivo inhibition of cysteine proteinases by EST, a new analog of E-64". Journal of Pharmacobio-Dynamics 9 (8): 672–7. August 1986. doi:10.1248/bpb1978.9.672. PMID 3023601.
- ↑ "Efficient synthetic method for ethyl (+)-(2S,3S)-3-[(S)-3-methyl- 1-(3-methylbutylcarbamoyl)butylcarbamoyl]-2-oxiranecarb oxylate (EST), a new inhibitor of cysteine proteinases". Chemical & Pharmaceutical Bulletin 35 (3): 1098–104. March 1987. doi:10.1248/cpb.35.1098. PMID 3301019.
- ↑ "Design, Synthesis, and Structure-Activity Relationship Study of Epoxysuccinyl-Peptide Derivatives as Cathepsin B Inhibitors". Biological & Pharmaceutical Bulletin 40 (8): 1240–1246. August 2017. doi:10.1248/bpb.b17-00075. PMID 28502922.
- ↑ "Therapeutic trials on progressive muscular dystrophy". Internal Medicine 31 (7): 841–6. July 1992. doi:10.2169/internalmedicine.31.841. PMID 1450492.
- ↑ "Cell death in spinal cord injury (SCI) requires de novo protein synthesis. Calpain inhibitor E-64-d provides neuroprotection in SCI lesion and penumbra". Annals of the New York Academy of Sciences 939: 436–49. June 2001. doi:10.1111/j.1749-6632.2001.tb03655.x. PMID 11462799.
- ↑ "Neurovascular and neuronal protection by E64d after focal cerebral ischemia in rats". Journal of Neuroscience Research 84 (4): 832–40. September 2006. doi:10.1002/jnr.20977. PMID 16802320.
- ↑ "Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease". The Journal of Clinical Investigation 118 (8): 2796–807. August 2008. doi:10.1172/JCI34254. PMID 18596919.
- ↑ "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". Journal of Alzheimer's Disease 26 (2): 387–408. 2011. doi:10.3233/JAD-2011-110101. PMID 21613740.
- ↑ "Brain pyroglutamate amyloid-β is produced by cathepsin B and is reduced by the cysteine protease inhibitor E64d, representing a potential Alzheimer's disease therapeutic". Journal of Alzheimer's Disease 41 (1): 129–49. 2014. doi:10.3233/JAD-131370. PMID 24595198.
- ↑ "Coronavirus protein processing and RNA synthesis is inhibited by the cysteine proteinase inhibitor E64d". Virology 208 (1): 1–8. April 1995. doi:10.1006/viro.1995.1123. PMID 11831690.
- ↑ "Host cell cathepsins potentiate Moloney murine leukemia virus infection". Journal of Virology 81 (19): 10506–14. October 2007. doi:10.1128/JVI.02853-06. PMID 17634228.
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