Protein kinase inhibitors are drugs that can inhibit the action of protein kinases. Protein kinases add a phosphate group to a protein to switch it on or off in a process known of as phosphorylation. In this way, protein kinases can therefore alter the function and activity of proteins and therefore cells.
Protein kinase inhibitors provide an important targeted therapy in several forms of cancers as well as several other diseases and disorders.
At present there are several drugs approved for use that target protein kinases and inhibit their actions.
Some examples of protein kinase inhibitors are described below:
- Bevacizumab – This is a monoclonal antibody that targets vascular endothelial growth factor A or VEGF-A. The trade name is Avastin and the drug was developed by Genentech/Roche. It was approved for the treatment of some metastatic cancers by the US FDA in 2004.
- Cetuximab – This is a chimeric monoclonal antibody that targets the epidermal growth factor receptor (EGFR) in the treatment of metastatic head and neck cancer and colon cancer. The drug is sold under the brand name Erbitux.
- Imatinib – This is tyrosine kinase inhibitor used to treat various different cancers, developed by Novartis and marketed under the name Gleevec.
- Trastuzumab – Also known of by its trade name herceptin, trastuzumab targets the HER2/neu receptor and is mainly used to treat breast cancer. This monoclonal antibody was developed by Genentech.
- Gefitinib – Marketed by AstraZeneca, this drug is an EGFR inhibitor used to treat some forms of breast cancer, lung cancer and other forms of cancer.
- Ranibizumab – This monoclonal antibody acts as an anti-angiogenic agent in the treatment of the “wet” (neovascular) form of age-related macular degeneration. This drug is sold under the trade name Lucentis.
- Pegaptanib - This is another anti-angiogenic agent used to treat the “wet” form of age-related macular degeneration. This drug was approved for this use by the US FDA in 2004.
- Sorafenib – Developed and marketed by Bayer and Onyx Pharmaceuticals, this kinase inhibitor is used to treat advanced renal cell carcinoma and hepatocellular carcinoma.
- Dasatinib - This is a tyrosine kinase inhibitor developed by Bristol-Myers Squibb and approved for use by the US FDA in 2006 for the treatment of chronic myelogenous leukemia.
- Sunitinib - This is a multi-targeted tyrosine kinase inhibitor developed by Pfizer and approved for use by the US FDA in 2006 for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor.
- Erlotinib - Erlotinib is a reversible tyrosine kinase inhibitor that acts on EGFR, to treat pancreatic cancer, non-small cell lung cancer and several other cancers.
- Nilotinib – Marketed under the trade name Tasigna, this small molecule tyrosine kinase inhibitor is used to treat imatinib-resistant chronic myelogenous leukemia.
- Lapatinib – This dual tyrosine kinase inhibitor targets both the EGFR and HER2/neu pathways and is used to treat breast cancer and some other solid tumors.
- Panitumumab – This monoclonal antibody targets EGFR, was manufactured by Amgen and is marketed as Vectibix.
- Vandetanib – This drug is a kinase inhibitor of several receptors including VEGFR, EGFR and the RET-tyrosine kinase in the treatment of some thyroid cancers. The drug was developed by AstraZeneca and marketed under the trade name Caprelsa.
- Pazopanib – This multi-targeted receptor tyrosine kinase inhibitor is used in the treatment of renal cell carcinoma and soft tissue carcinoma.
Reviewed by Sally Robertson, BSc