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

DrugTarget
AbemaciclibCyclin dependent kinase (CDK) 4/6
AcalabrutinibBruton’s kinase
AfatinibEGFR2, HER2
AlectinibALK
AlpelisibPI3K
AsciminibBCR-ABL
AvapritinibPI3K
AxitinibVEGFR 1-3, c-KIT, PDGF
BinimetinibBRAF
BosutinibBCR-ABL, SCR, c-Kit, PDGF, VEGF
BrigatinibALK
CabozantinibMET, VEGFR-2 , RET
CapmatinibMET
CeritinibALK
CobimetinibMEK
CopanlisibPI3K, ALK
CrizotinibMET
DacomitinibHER1, 2, 3
DasatinibBCR-ABL, SCR, c-Kit
DuvelisibPI3K
EncorafenibBRAF
EntrectinibNTRK
ErdafitinibFGFR
ErlotinibEGFR, HER1
GefitinibEGFR
GilteritinibFLT3
IbrutinibBruton’s kinase
IdelalisibPI3K
ImatinibBCR-ABL, c-Kit
InfigratinibFGFR
LapatinibEGFR, HER2
LarotrectinibTRK
LenvatinibVEGFR 1-3, FGF 1-4, PDGF, c-Kit, RET
LorlatinibALK
MidostaurinFLT3
MobocertinibEGFR
NeratinibHER2
NilotinibBCR-ABL. PDGF, cKit
OsimertinibEGFR
PalbociclibER+, HER2, Cyclin dependent kinase
PazopanibVEGFR 1-3, c-KIT
PemigatinibFGFR
PonatinibBCR-ABL, scr, c-Kit and ephrin
PralsetinibRET
RegorafenibVEGFR 1-3, PDGF, RAF, c-Kit and TIE2.
RibociclibCyclin dependent kinase 4/6
RipretinibKit and PDGFR
RuxolitinibJanus kinase
SelpercatinibRET
SorafenibVEGFR 1-3 , PDGF
SotorasibKRAS
SunitinibPDGF, c-Kit, VEGFR
TabrectaMET
TepotinibRAS–RAF and PI3K–AKT
TivozanibVEGFR
TrametinibMEK 1-2
TucatinibPDGFR and KIT
UmbralisibPI3K
VandetanibVEGFR 2 , EGF, RET, BRK, and Src
VenetoclaxBCL-2
VemurafenibBRAF
ZanubrutinibBruton’s kinase
Ziv-afliberceptVEGF

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 targetDrugs
AblPonatinib
ALKAlectinib
AXLGilteritinib
BCL-2Venetoclax
Bcr-ACLBosutinib Imatinib Nilotinib Radotinib
BRAFDabrafenib Vemurafenib
Bruton’s Tyrosine KinaseAcalabrutinib Ibrutinib Zanubrutina
c-KitAxitinib Cabozantinib Imatinib Pazopanib Ripretinib Tucatinib
CDK4/6Abemaciclib Palbociclib Ribocicilib
EGFRAfatinib Brigatinib Dacomitinib Erlotinib Gefitinib Lapatinib Mobocertinib Neratinib
FGFRPemigatinib Infigratinib
FLT3Gilteritinib Midostaurin
HER2Afatinib
JAKRuxolitinib Tofacitinib
KRASSotorasib
MEK1/2Cabozantinib Ripretinib Tucatinib Midostaurin
METCrizotinib Tabrecta
mTORCopanlisib Everolimus Sirolimus Temsirolimus
Multiple Tyrosine Kinases TargetedDasatinib Soraferib Sunitinib Vandetanib
NTRKLarotrectinib Entrectinib
PDGFRAxitinib Cabozantinib Imatinib Pazopanib Radotinib Tucatinib
PI3KAlpelisib Avapritinib Copanlisib Duvelisib Idelalisib Umbralisib
RAFBinimetinib Encorafenib
RETPralsetinib Selpercatinib
ROSEntrectinib Loratinib
SRCBosutinib Dasatinib Ponatinib
VEGFRAxitinib Cabozantinib Catequenetinib Lenvatinib Pazopanib Regorafenib Tivozanib

Drug Targets and corresponding protein substrate

Mechanisms of kinase inhibitors