Kinase inhibitors are designed to go after specific mutations that drive tumorigenesis. There are more than 500 kinases and approved cancer drugs work on more than 40 of them. Each drug may target more than one kinase; these multikinase inhibitors are less targeted and hence more likely to be toxic, but the upside is that they can often be used for more than one types of cancer.

(Multikinase inhibitors have been called “dirty targeted” drugs because they are less focused, but there may be advantages to dirty drugs.)

About Kinases

Kinases are proteins and enzymes. They catalyze the transfer of phosphate groups to proteins and are important in many cell functions.  Kinases are important in many physiological functions.  The kinase superfamily has 555 proteins; of these 497 are eukaryotic and 58 are prokaryotic.

Kinases convey extracellular signals to affect the direction of the cell, and hence they play a part in tumor growth.  Mutations that result in overexpressed kinases play a part in many diseases.  Aurora kinases play an important part in spindle formation in mitosis.  Kinase inhibition is a major thrust in new pharmaceutical development; observers estimate that kinases are a third of all protein targets in drug research today.

List of Kinase Inhibitors

What do these acronyms mean?

ALK – anaplastic lymphoma kinase
AXL – a gene that encodes the tyrosine-protein kinase receptor UFO. from the Greek word “anexelekto” which means uncontrolled. AXL is a biomarker due to its role in tumorigenesis
BCL-2 – B-cell lymphoma 2
Bcr-ACL – gene sequence present in cells of some people with leukemia. The presence of the gene sequence known as BCR-ABL1 confirms the diagnosis of CML and a form of acute lymphoblastic lymphoma (ALL)
BRAF – gene, aka B-Raf, which makes the B-Raf protein that is involved in sending signals in cells and in cell growth. The mutated BRAF gene is found in some types of cancer
c-Kit – stem cell factor receptor that comes from the oncogene Kit
EGFR – epidermal growth factor receptor
FGFR – fibroblast growth factor receptor
HER2 – human epidermal growth factor receptor, aka ER882
JAK – Janus kinases – formerly “just another kinase”, aka jakinibs
KRAS – Kirsten rat sarcoma viral oncogene homolog
MEK – mitogen-activated extracellular regulated kinase
MET – hepatocyte growth factor receptor (HGFR) aka c-MET.
mTOR – mechanistic target of rapamycin
NTRK – neurotrophic tyrosine receptor kinase
PI3K – phosphatidylinositol 3-kinase
PDGFR – platelet derived growth factor receptor
RET – rearranged during transfection
ROS – reactive oxygen species
TRK – tropomyosin receptor kinases
VEGFR – vascular endothelial growth factor receptor

Grouped by Target

Drug Targets and corresponding protein substrate

Mechanisms of kinase inhibitors