| Bioactivity | E 64c is a derivative of naturally occurring epoxide inhibitor of cysteine proteases, a Calcium-activated neutral protease (CANP) inhibitor and a very weak irreversible cathepsin C inhibitor. E 64c exhibits entry-blocking effect for MERS-CoV. | ||||||||||||
| Target | Cysteine proteases, CANP, Cathepsin C. | ||||||||||||
| Invitro | E-64c, a derivative of naturally occurring epoxide inhibitor of cysteine proteases, with papain; especially with regard to the hydrogen bonding and hydrophobic interactions of the ligands with conserved residues in the catalytic binding site[1]. E 64c (k2/Ki=140±5M-1s-1) is demonstrated to be a lead structure for the development of irreversible cathepsin C inhibitors[3]. | ||||||||||||
| In Vivo | The t-1/2 of plasma E-64c is 0.48 hours. The hemodynamic effects of E-64c are absent at this dose. Using two way analysis of variance, the effects of reperfusion (p=0.0016) or E-64c (p=0.0226) per se on infarct size are significant. In comparing Group A with Group B and Group C with Group D, the depletion of CPK in the E-64c treated groups (Groups A and C) is slightly less than in the vehicle-injected groups (Groups B and D). The insufficient effect of E-64c alone may be explained by the early administration and relatively short t-1/2. Since the effectiveness of NCO-700 has been established,6),7) our findings might indicate a small but beneficial effect of E-64c on infarct size and CPK content[2]. | ||||||||||||
| Name | E 64c | ||||||||||||
| CAS | 76684-89-4 | ||||||||||||
| Formula | C15H26N2O5 | ||||||||||||
| Molar Mass | 314.38 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Khan MS, et al. Design, synthesis, evaluation and thermodynamics of 1-substituted pyridylimidazo[1,5-a]pyridine derivatives as cysteine protease inhibitors. PLoS One. 2013 Aug 5;8(8):e69982. [2]. Toda G, et al. Calcium-activated neutral protease inhibitor (E-64c) and reperfusion for experimental myocardial infarction. Jpn Heart J. 1989 May;30(3):375-86. [3]. Radzey H, et al. E-64c-hydrazide: a lead structure for the development of irreversible cathepsin C inhibitors. ChemMedChem. 2013 Aug;8(8):1314-21. [4]. Ji Yeun Kim, et al. Safe, High-Throughput Screening of Natural Compounds of MERS-CoV Entry Inhibitors Using a Pseudovirus Expressing MERS-CoV Spike Protein. Int J Antimicrob Agents. 2018 Nov;52(5):730-732. |