Methods for designing inhibitors of serine/threonine kinases...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/54 (2006.01) C12N 9/12 (2006.01) C12Q 1/48 (2006.01)

Patent

CA 2321184

The invention relates to methods for designing inhibitors of serine/threonine kinases and tyrosine kinases, particularly MAP kinases, through the use of ATP- binding site mutants of those kinases. The methods of this invention take advantage of the fact that the mutant kinases are capable of binding inhibitory compounds of other kinases with greater affinity than the corresponding wild-type kinase. The invention further relates to the mutant kinases themselves and crystallizable co-complexes of the mutant kinase and the inhibitory compound.

L'invention concerne des procédés servant à développer des inhibiteurs de sérine/thréonine kinases et de tyrosine kinases, en particulier des MAP kinases, au moyen de mutantes du site de fixation à ATP de ces kinases. Ces procédés sont avantageusement basés sur le fait que les kinases mutantes sont capables de se fixer à des composés inhibiteurs d'autres kinases avec une affinité supérieure à celle de la kinase correspondante de type sauvage. Elle concerne, de plus, les kinases mutantes proprement dites et des complexes associés cristallisables de la kinase mutante et du composé inhibiteur.

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