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.