Abstract
Deregulation of the receptor tyrosine kinase c-Kit is associated with an increasing number of human diseases, including certain cancers and mast cell diseases. Interference of c-Kit signaling with multi-kinase inhibitors has been shown clinically to successfully treat gastrointestinal stromal tumors and mastocytosis. Targeted therapy of c-Kit activity may provide therapeutic advantages against off-target effects for non-oncology applications. A new structural class of c-Kit inhibitors is described, including in vitro c-Kit potency, kinase selectivity, and the observed binding mode.
MeSH terms
-
Amides / chemical synthesis*
-
Amides / chemistry
-
Amides / pharmacology*
-
Combinatorial Chemistry Techniques
-
Crystallography, X-Ray
-
Humans
-
Isoxazoles / chemical synthesis*
-
Isoxazoles / chemistry
-
Isoxazoles / pharmacology*
-
Molecular Conformation
-
Molecular Structure
-
Proto-Oncogene Proteins c-kit / drug effects*
-
Proto-Oncogene Proteins c-kit / metabolism*
-
Receptor Protein-Tyrosine Kinases / metabolism
-
Structure-Activity Relationship
-
p38 Mitogen-Activated Protein Kinases / drug effects
Substances
-
Amides
-
Isoxazoles
-
Proto-Oncogene Proteins c-kit
-
Receptor Protein-Tyrosine Kinases
-
p38 Mitogen-Activated Protein Kinases