METHOD FOR DIRECT INHIBITION OF CASPASE ACTIVITY Russian patent published in 2004 - IPC

FIELD: biotechnology, enzymology.

SUBSTANCE: invention relates to inhibition of activity of cysteine aspartate-specific proteases (caspases) and can be used in biochemistry, cellular biology, physiology and pharmacology for investigation and directed regulation of processes associated with induction, development of prevention of the scheduled cellular death (apoptosis) and for study of structure and mechanism action of caspases. Method is carried out by addition to medium containing activated caspases the anellated derivatives of 1,2-isoselenazol-3-one of the general formula [1] indicated in the invention claim wherein: if X means C-O-CH₃, C-O-(O)-CH₃, C-NO₂ or N then R means C₆H₅; or if X means CH then R means carboxymethyl; unsubstituted phenyl or phenyl comprising at position 4 chlorine atom, nitro-, carboxy- or (C₁-C₄)-oxycarbonyl group; α-methylbenzyl; α-methyl-[(lower alkyl)oxycarbonyl]methyl; pyridyl or (pyridyl)methyl, or its biochemically acceptable salt. Invention provides effective reducing activity of these enzymes in the presence of other proteins (for the most related known derivative of isatin the value IC₅₀ = 7.5 ± 3.5 mcM) in the presence of compounds used in the described method, in particular, 10 mcM of 2-phenyl-1,2-benzisoselenazol-3-one activity of caspase-3 (+ caspase-7) was found to be 7.53 ± 2.5% of the initial value.

EFFECT: improved inhibition method.

1 ex