Relevance of kinase mutants
Protein kinases are ranked among the most interesting targets in cancer. Several protein kinase inhibitors have been successfully developed as anti-cancer drugs and are approved for the treatment of different forms of cancer. One challenge of protein kinase inhibitors in the treatment of patients is the occurrence of inhibitor-resistant mutant forms of the target protein kinase. Therefore, studying the inhibitory effect of established and new inhibitors not only against the wild type but in addition against different mutant forms of a kinase is of significant relevance in the drug development process. ProQinase offers one of the largest collection of human mutant protein kinases, and its Kinase MutantProfilers as service.

Study example
The study example shows the inhibitory IC50 profile of the well established inhibitor Vargatef against wild type and nine different mutant forms of the RET.  All proteins have been expressed and purified as GST-fusion proteins and are identical with respect to the amino acid sequence except of the mutation introduced.

Structure and pathophysiological mutations of the human EGF-R
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Inhibition of wt RET and nine mutants by Vargatef
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10

 Gefitinib (Iressa®)

 MET MutantProfiler

9

 PHA665752