Use of a kinase inhibitor for the treatment of particular resistant tumors

A method of treating BCR-ABL inhibitor-resistant T3151 ABL-mediated disease, which comprises administering to a mammal in need thereof an effective amount of the compound of formula (II)

• wherein R4 is a group selected from azetidin-1-yl, pirrolidin-1-yl, piperidin-1-yl, (1-methyl-piperazin-4-yl), (morpholino-4-yl), (azetidin-1-yl)methyl, (pirrolidin-1-yl)methyl, (piperidin-1-yl)methyl, (1-methyl-piperazin-4-yl)methyl, (morpholino-4-yl)methyl, (1-methyl-piperidin-4-yloxy)methyl, (isopropyl amino)methyl;
• and
• R3 is a hydrogen or fluorine or chlorine atom.

A screening method for the identification of compounds capable of binding the ATP pocket of a kinase protein, comprising the steps of:

• providing a reaction mixture comprising the kinase protein, an indolinone having affinity for the ATP pocket of the said kinase protein and capable of generating a fluorescent signal upon binding to the said ATP pocket, and serial dilutions of the test compound, comparing the fluorescent signal generated in the absence of the test compound with the fluorescent signal generated in the presence of different concentrations of the test compound, whereby a decreased level of fluorescence indicates the ability of the test compound to displace the indolinone.

A method for inhibiting a BCR-ABL inhibitor-resistant tyrosine kinase activity comprising contacting a BCR-ABL inhibitor-resistant tyrosine kinase polypeptide with an effective amount of the compound of formula (II)

• wherein R4 is a group selected from azetidin-1-yl, pirrolidin-1-yl, piperidin-1-yl, (1-methyl-piperazin-4-yl), (morpholino-4-yl), (azetidin-1-yl)methyl, (pirrolidin-1-yl)methyl, (piperidin-1-yl)methyl, (1-methyl-piperazin-4-yl)methyl, (morpholino-4-yl)methyl, (1-methyl-piperidin-4-yloxy)methyl, (isopropyl amino)methyl;
• and
• R3 is a hydrogen or fluorine or chlorine atom.