Kinase mutants and uses thereof
AssigneesSIB Swiss Institute of Bioinformatics, CHUV—Centre Hospitalier Universitaire Vaudois, Universite de Lausanne, Ludwig Institute for Cancer Research
InventorsOlivier Michielin, Vincent Zoete, George Coukos, Melita Irving, Nahzli Dilek, Patrick Reichenbach, Kelly Ascencao
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Abstract
The present invention relates to methods of designing kinase mutants for reprogramming the sensitivity of a target kinase to some specific inhibitors, methods of reprogramming the sensitivity of a target kinase to some specific inhibitors, wherein those kinase inhibitors have little or no affinity for the wild-type target kinase, vectors or cells expressing said mutated kinases, composition and uses thereof for the prevention and/or treatment of a disease or disorder, in particular cancer.
Claims18
-29. (canceled)
An isolated nucleic acid molecule encoding a Zap-70 kinase mutant that retains functional activity of wild-type Zap-70 kinase and is more sensitive than wild-type Zap-70 kinase to inhibition by erlotinib and vandetanib, wherein the Zap-70 kinase mutant comprises an amino acid sequence of SEQ ID NO:
- 1 wherein is introduced at least one mutation selected from:
- V399I, M414A, M414T, M414V, M416Y, M416V, M416L, M416I, M416F, M416W, M416H, M416T, and M416S.
An isolated nucleic acid molecule encoding a Zap-70 kinase mutant that retains functional activity of wild-type Zap-70 kinase and is more sensitive than wild-type Zap-70 kinase to inhibition by erlotinib and vandetanib, wherein the Zap-70 kinase mutant comprises an amino acid sequence selected from SEQ ID NO:
- 3, SEQ ID NO:
- 4, SEQ ID NO:
- 5, SEQ ID NO:
- 6, SEQ ID NO:
- 7, and SEQ ID NO:
- 8.
Dependencies are inferred from the claim text.