Use of tyrosine kinase inhibitors for treating cerebral ischemia
AssigneeScience Incorporated
InventorsJean-Pierre Kinet, Alain Moussy
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Abstract
The present invention relates to a method for treating cerebral ischemia, comprising administering a compound capable of depleting mast cells or a compound inhibiting mast cells degranulation to a human in need of such treatment. Such compounds can be chosen from tyrosine kinase inhibitors and more particularly non-toxic, selective and potent c-kit inhibitors. Preferably, said inhibitor is unable to promote death of IL-3 dependent cells cultured in presence of IL-3.
Claims27
A method for treating cerebral ischemia comprising administering a compound capable of depleting mast cells or inhibiting mast cell degranulation to a human in need of such treatment.
4-26. (canceled)
A method for treating and/or preventing or delaying renal cerebral ischemia comprising administering to a human in need of such treatment a compound that is a selective, non toxic inhibitor of activated c-kit obtainable by a screening method which comprises:
- (a) bringing into contact (i) activated c-kit and (ii) at least one compound to be tested;
- under conditions allowing the components (i) and (ii) to form a complex,
- (b) selecting compounds that inhibit activated c-kit,
- (c) testing and selecting a subset of compounds identified in step b), which are unable to promote death of IL-3 dependent cells cultured in the presence of IL-3.
A method for treating and/or preventing or delaying cerebral ischemia comprising administering to a human in need of such treatment a c-kit inhibitor obtainable by a screening method comprising:
- (a) performing a proliferation assay with cells expressing a mutant c-kit, which mutant is a permanent activated c-kit, with a plurality of test compounds to identify a subset of candidate compounds targeting activated c-kit, each compound having an IC50 of less than 19 μM, by measuring the extent of cell death;
- (b) performing a proliferation assay with cells expressing c-kit wild and the subset of candidate compounds identified in step (a), the cells being IL-3 dependent cells cultured in the presence of IL-3, to identify a subset of candidate compounds specifically targeting c-kit;
- (c) performing a proliferation assay with cells expressing c-kit and the subset of compounds identified in step (b) and selecting a subset of candidate compounds targeting c-kit wild, each having an IC50<10 μM, by measuring the extent of cell death.
Dependencies are inferred from the claim text.