Types 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 have more than one target.

List of Kinase Inhibitors

Drug Target
Abemaciclib Cyclin dependent kinase (CDK) 4/6
Acalabrutinib Bruton’s kinase
Afatinib EGFR2, HER2
Alectinib ALK
Alpelisib PI3K alpha (α)
Avapritinib PI3K delta (δ)
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
Ceritinib ALK
Cobimetinib MEK
Copanlisib PI3Kα/δ
Crizotinib ALK
Dabrafenib BRAF
Dacomitinib HER1,2,3
Dasatinib BCR-ABL, scr, c-Kit, ephrin
Duvelisib PI3K
Encorafenib BRAF
Entrectinib
Erdafitinib
Erlotinib EGFR, HER1
Gefitinib EGFR
Gilteritinib FLT3
Ibrutinib Bruton kinase
Idelalisib PI3Kδ
Imatinib BCR-ABL, c-Kit
Lapatinib EGFR, HER2
Larotrectinib
Lenvatinib VEGFR 1-3, FGF 1-4, PDGF, c-Kit, RET
Lorlatinib ALK
Midostaurin FLT3
Neratinib HER2
Nilotinib BCR-ABL. PDGF, cKit
Osimertinib EGFR
Palbociclib ER+, HER2, Cyclin dependent kinase
Pazopanib VEGFR 1-3, c-KIT
Pemigatinib
Ponatinib BCR-ABL, scr, c-Kit and ephrin
Pralsetinib
Regorafenib VEGFR 1-3, PDGF, RAF, c-Kit and TIE2.
Ribociclib Cyclin dependent kinase 4/6
Ripretinib
Ruxolitinib Janus kinase
Selpercatinib RET
Sorafenib VEGFR 1-3 , PDGF
Sunitinib PDGF, c-Kit, VEGFR
Tepotinib RAS–RAF and PI3K–AKT
Tivozanib VEGFR
Trametinib MEK 1-2
Tucatinib PDGFR and KIT
Umbralisib PI3Kδ and casein kinase-1ε
Vandetanib VEGFR 2 , EGF, RET, BRK, and Src
Vemurafenib BRAF
Zanubrutinib Bruton’s kinase
Ziv-aflibercept

What do these acronynms 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 biological processes and tumourigenesis
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, which makes a protein that is involved in sending signals in cells and in cell growth. The mutated BRAF gene is found in some types of cancer
cKit – abnormal tyrosine kinase
EGFR – epidermal growth factor receptor
FGFR – fibroblast growth factor receptor
HER2 – human epidermal growth factor receptor, aka ER882
JAK – just another kinase
MEK – mitogen-activated extracellular regulated kinase
MET – hepatocyte growth factor receptor
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
VEGFR – vascular endothelial growth factor receptor

Grouped by Target

Drug target Drugs
Abl
ALK
AXL
Bcr-ACL
BRAF
Bruton’s Tyrosine Kinase
cKit
CDK4/6
EGFR
FGFR/FGFR2
FLT3
HER2
JAK
kit
MEK1/2
MET
mTOR
Multiple Tyrosine Kinases Targeted
NTRK
PDGFR
PI3K
RAF
RET
ROS
SRC
TRK
VEGFR

About Kinases

Kinases are proteins and enzymes. They catalyze the transfer of phosphate groups to proteins and are important in many cell functions. Some kinases play a role in the growth of tumors. Other kinases are overexpressed in tumors. Others called aurora kinases play an important part in spindle formation in mitosis.

Type I vs Type II

Medicinal chemists can classify kinase inhibitors by how they work at the molecular level. Type I is ““a small molecule that binds to the active conformation of a kinase in the ATP pocket,” Type II is “a small molecule that binds to an inactive (usually Asp-Phe-Gly (DFG)-OUT) confirmation of a kinase,” and the type III inhibitor as “a non-ATP competitive inhibitor” or allosteric inhibitor.

Growth Factor inhibitors

HER2 inhibitor drugs include pertuzumab, rastuzumab, neratinib, lapatinib, ado-trastuzumab emtansine, and dacomitinib.  EGFR inhibitors include gefitinib, neratinib, panitumumab, erlotinib, lapatinib, cetuximab, osimertinib, vandetanib, necitumumab, and dacomitinib.

VEGF/VEGFR inhibitors include pazopanib, sorafenib, ponatinib, bevacizumab, ziv-aflibercept, sunitinib, cabozantinib, axitinib, regorafenib, cabozantinib, vandetanib, ramucirumab, lenvatinib, and bevacizumab.