Kinase modulation and indications therefor
Compounds, compositions and methods useful for treatment of Flt3-mediated diseases or conditions are provided herewith. Also provided herewith are methods for modulating the receptor protein tyrosine like kinase 3(Flt3).
1. A method for treating a subject suffering from acute myeloid leukemia (AML), said method comprising administering to the subject an effective amount of a compound having the formula:
or a pharmaceutically acceptable salt, tautomer or isomer thereof, wherein the subject has an FMS-like tyrosine kinase (Flt3) gene with an internal tandem duplication (ITD) mutation.
2. The method of claim 1 , wherein the Flt3 gene further comprises an amino acid substitution at residues F691, D835, Y842 or combinations thereof.
3. The method of claim 2 , wherein the amino acid substitution is selected from F691L, D835V/Y, Y842C/H and combinations thereof.
4. The method of claim 3 , wherein the amino acid substitution comprises F691L.
5. The method of claim 1 , wherein the administration is oral.
6. The method of claim 1 , wherein the effective amount is 0.1 mg/kg to 20 mg/kg.