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.  Regorafenib has action against 14 different kinases.

List of Kinase Inhibitors

Drug Target
Abemaciclib Cyclin dependent kinase 4/6
Acalabrutinib Bruton kinase
Afatinib EGFR2, HER2
Alectinib ALK
Axitinib VEGFR 1-3, c-KIT, PDGF
Binimetinib BRAF
Bosutinib BCR-ABL, scr, c-Kit, PDGF, VEGF
Brigatinib ALK
Cabozantinib MET, VEGFR-2 , RET
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
Erlotinib EGFR, HER1
Gefitinib EGFR
Gilteritinib FLT3
Ibrutinib Bruton kinase
Idelalisib PI3Kδ
Imatinib BCR-ABL, c-Kit
Lapatinib EGFR, HER2
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
Ponatinib BCR-ABL, scr, c-Kit and ephrin
Regorafenib VEGFR 1-3, PDGF, RAF, c-Kit and TIE2.
Ribociclib Cyclin dependent kinase 4/6
Ruxolitinib Janus kinase
Sorafenib VEGFR 1-3 , PDGF
Sunitinib PDGF, c-Kit, VEGFR
Trametinib MEK 1-2
Vandetanib VEGFR 2 , EGF, RET, BRK, and Src
Vemurafenib BRAF

BRK – Breast Tumor Kinase
cKit – abnormal tyrosine kinase
EGFR – epidermal growth factor receptor
FGF – fibroblast growth factor
HER – human epidermal growth factor receptor
MAPK – an important component of the kinase cascade in the mitogen activated protein kinase
MEK – mitogen-activated extracellular regulated kinase
MET – hepatocyte growth factor receptor
PI3K – phosphatidylinositol 3-kinase
PDGFR – platelet derived growth factor receptor
RET – rearranged during transfection
VEGFR – vascular endothelial growth factor receptor

Grouped by Target

Tyrosine Kinases

Drug target Drugs
ALK Alectinib, Brigatinib, Ceritinib, Crizotinib, Lorlatinib
BCR-ABL Bosutinib, Dasatinib, Imatinib, Nilotinib, Ponatinib
Bruton kinase Ibrutinib, Acalabrutinib
C-Kit Axitinib, Bosutinib, Dasatinib. Imatinib, Lenvatinib, Pazopanib, Ponatinib, Regorafenib, Sunitinib
EGFR Afatinib, Erlotinib, Gefitinib Lapatinib Osimertinib
FLT3 Gilteritinib, Midostaurin
HER Afatinib, Dacomitinib, Erlotinib, Lapatinib, Neratinib, Palbociclib
Janus kinase Ruxolitinib
RET Cabozantinib, Lenvatinib, Vandetanib
PDGF Axitinib, Bosutinib, Lenvatinib, Nilotinib, Regorafenib, Sorafenib, Sunitinib
VEGFR Axitinib, Cabozantinib, Lenvatinib, Pazopanib, Regorafenib, Sorafenib, Sunitinib, Vandetanib

Ser/Thr kinases

Drug target Drugs
BRAF Binimetinib, Dabrafenib, Encorafenib, Vemurafenib
CDK Abemaciclib, Ribociclib, Palbociclib

About Kinases

Kinases are proteins and enzymes.  They catalyze the transfer phosphate groups to proteins and are important in many cell functions.   Some kinases play a role in development of cancers.  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.