Targets of Kinase Inhibitors

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.

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.

Mutations that result in overexpressed kinases play a part in many diseases.  Some kinases play a role in the growth of tumors. Others called 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

Drug Target
Abemaciclib Cyclin dependent kinase (CDK) 4/6
Acalabrutinib Bruton’s kinase
Afatinib EGFR2, HER2
Alectinib ALK
Alpelisib PI3K
Avapritinib PI3K
Axitinib VEGFR 1-3, c-KIT, PDGF
Binimetinib BRAF
Bosutinib BCR-ABL, SCR, c-Kit, PDGF, VEGF
Brigatinib ALK
Cabozantinib MET, VEGFR-2 , RET
Capmatinib MET
Ceritinib ALK
Cobimetinib MEK
Copanlisib PI3K, ALK
Crizotinib MET
Dacomitinib HER1, 2, 3
Dasatinib BCR-ABL, SCR, c-Kit
Duvelisib PI3K
Encorafenib BRAF
Entrectinib NTRK
Erdafitinib FGFR
Erlotinib EGFR, HER1
Gefitinib EGFR
Gilteritinib FLT3
Ibrutinib Bruton’s kinase
Idelalisib PI3K
Imatinib BCR-ABL, c-Kit
Infigratinib FGFR
Lapatinib EGFR, HER2
Larotrectinib TRK
Lenvatinib VEGFR 1-3, FGF 1-4, PDGF, c-Kit, RET
Lorlatinib ALK
Midostaurin FLT3
Mobocertinib EGFR
Neratinib HER2
Nilotinib BCR-ABL. PDGF, cKit
Osimertinib EGFR
Palbociclib ER+, HER2, Cyclin dependent kinase
Pazopanib VEGFR 1-3, c-KIT
Pemigatinib FGFR
Ponatinib BCR-ABL, scr, c-Kit and ephrin
Pralsetinib RET
Regorafenib VEGFR 1-3, PDGF, RAF, c-Kit and TIE2.
Ribociclib Cyclin dependent kinase 4/6
Ripretinib Kit and PDGFR
Ruxolitinib Janus kinase
Selpercatinib RET
Sorafenib VEGFR 1-3 , PDGF
Sotorasib KRAS
Sunitinib PDGF, c-Kit, VEGFR
Tabrecta MET
Tepotinib RAS–RAF and PI3K–AKT
Tivozanib VEGFR
Trametinib MEK 1-2
Tucatinib PDGFR and KIT
Umbralisib PI3K
Vandetanib VEGFR 2 , EGF, RET, BRK, and Src
Venetoclax BCL-2
Vemurafenib BRAF
Zanubrutinib Bruton’s kinase
Ziv-aflibercept VEGF

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 target Drugs
Abl Ponatinib
ALK Alectinib
AXL Gilteritinib
BCL-2 Venetoclax
Bcr-ACL Bosutinib Imatinib Nilotinib Radotinib
BRAF Dabrafenib Vemurafenib
Bruton’s Tyrosine Kinase Acalabrutinib Ibrutinib Zanubrutina
c-Kit Axitinib Cabozantinib Imatinib Pazopanib Ripretinib Tucatinib
CDK4/6 Abemaciclib Palbociclib Ribocicilib
EGFR Afatinib Brigatinib Dacomitinib Erlotinib Gefitinib Lapatinib Mobocertinib Neratinib
FGFR Pemigatinib Infigratinib
FLT3 Gilteritinib Midostaurin
HER2 Afatinib
JAK Ruxolitinib Tofacitinib
KRAS Sotorasib
MEK1/2 Cabozantinib Ripretinib Tucatinib Midostaurin
MET Crizotinib Tabrecta
mTOR Copanlisib Everolimus Sirolimus Temsirolimus
Multiple Tyrosine Kinases Targeted Dasatinib Soraferib Sunitinib Vandetanib
NTRK Larotrectinib Entrectinib
PDGFR Axitinib Cabozantinib Imatinib Pazopanib Radotinib Tucatinib
PI3K Alpelisib Avapritinib Copanlisib Duvelisib Idelalisib Umbralisib
RAF Binimetinib Encorafenib
RET Pralsetinib Selpercatinib
ROS Entrectinib Loratinib
SRC Bosutinib Dasatinib Ponatinib
VEGFR Axitinib Cabozantinib Catequenetinib Lenvatinib Pazopanib Regorafenib Tivozanib

Drug Targets and corresponding protein substrate

Mechanisms of kinase inhibitors