Beneficial effect of new thiol protease inhibitors, epoxide derivatives, on dystrophic mice.
We studied the effect of E-64, a new thiol protease inhibitor derived from Aspergillus japonicus TPR-64, and of its synthesized analogue, E-64-d, on dystrophic mice (C57BL/6J-dy). The locomotor activity of normal mice increased markedly, reaching a plateau at 8 weeks of age. In dystrophic mice, it increased until they were 7 weeks old, thereafter, it decreased gradually. This decrease reflected the degradation of the hind legs. Serum activities of creatine phosphokinase were significantly greater in dystrophic than in normal mice. When 3-week-old dystrophic mice were injected with E-64 (1 mg/kg, i.p.) or E-64-d (40 to 60 mg/kg, p.o.), the decrease in their locomotor activity was retarded and their serum enzyme activities decreased significantly. In addition, the survival time of treated dystrophic mice was prolonged. The locomotor activity of normal mice and their serum enzyme levels were not affected by the administration of E-64-d. We posit that the new thiol protease inhibitors we tested retard the progression of dystrophy in mice.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003402:Creatine Kinase / Q000097:blood; D007930:Leucine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality
D003402:Creatine Kinase; D007930:Leucine; C108192:aloxistatin; C024974:E 64