Protein kinase inhibitor
A protein kinase inhibitor is a type of enzyme inhibitor that blocks the action of one or more protein kinases. Protein kinases are enzymes that add a phosphate (PO4) group to a protein or other organic molecule. Phosphate groups can turn a protein off.
The phosphate groups are usually added to the serine, threonine, or tyrosine amino acid on the protein. Hence, protein kinase inhibitors can be subdivided or characterised by the amino acids whose phosphorylation is inhibited: most kinases act on both serine and threonine, the tyrosine kinases act on tyrosine, and a number (dual-specificity kinases) act on all three. There are also protein kinases that phosphorylate other amino acids, including histidine kinases that phosphorylate histidine residues.
Phosphorylation is a necessary step in some cancers and inflammatory diseases. Inhibiting the protein kinases, and therefore the phosphorylation, can treat these diseases. Therefore, protein kinase inhibitors are used as drugs.
Kinase inhibitors such as dasatinib are often used in the treatment of cancer and inflammation. The novel kinase inhibitor PLX5568 is currently in clinical trials for treatment of polycystic kidney disease as well as pain.
Currently there are several drugs launched or in development that target protein kinases and the receptors that activate them:
|Afatinib||EGFR/ErbB2||Boehringer Ingelheim||Small molecule||2013 Non-small cell lung cancer|
|Axitinib||VEGFR1/VEGFR2/VEGFR3/PDGFRB/c-KIT||Pfizer||Small molecule||2012 Renal cell carcinoma|
|Bevacizumab||VEGF||Genentech||Monoclonal antibody||2004 Colorectal|
|Bosutinib||BcrAbl /SRC||Pfizer||Small molecule||2012 Chronic myelogenous leukemia|
|Cetuximab||ErbB1||Imclone/BMS||Monoclonal antibody||2006 Mar (SCCHN)|
|Crizotinib||ALK/Met||Pfizer||Small molecule||2011 Aug (NSCLC with Alk mutation)|
|Dasatinib||multiple targets||BMS||Small molecule||2006|
|Erlotinib||ErbB1||Genentech||Small molecule||2005 Nov ?|
|Fostamatinib||Syk||Rigel Pharmaceuticals/AstraZeneca||Small molecule||Not yet |
|Imatinib||Bcr-Abl||Novartis||Small molecule||2001 (CML), 2002 (GIST) |
|Lapatinib||ErbB1/ErbB2||GSK||Small molecule||2007 (HER2+ Breast)|
|Lenvatinib||VEGFR2/VEGFR2||Eisai Co.||Small molecule||Not yet|
|Mubritinib||?||Takeda||Small molecule||Not yet, possibly abandoned|
|Pazopanib||VEGFR2/PDGFR/c-kit||GlaxoSmithKline||Small molecule||2009 (RCC)|
|Pegaptanib||VEGF||OSI/Pfizer||RNA Aptamer||2004 (AMD)|
|Ranibizumab||VEGF||Genentech||Monoclonal antibody||2006 (AMD)|
|Ruxolitinib||JAK||Incyte||Small molecule||2011 (Myelofibrosis)|
|Sorafenib||multiple targets||Onyx/Bayer||Small molecule||2005 Dec (kidney)|
|Sunitinib||multiple targets||SUGEN/Pfizer||Small molecule||2006 Jan (RCC & GIST)|
|SU6656||multiple targets||SUGEN||Small molecule||2000 Jan (RCC & GIST)|
|Trastuzumab||Erb2||Genentech||Monoclonal antibody||1998 (HER2+ breast cancer)|
|Tofacitinib||JAK||Pfizer||Small molecule||2012 Nov (RA)|
|Vandetanib||RET/VEGFR/EGFR||AstraZeneca||Small molecule||No, submission withdrawn Oct09 |
|Vemurafenib||BRAF||Roche||Small molecule||2011 Aug Melanoma|
- Protein kinase inhibitors at the US National Library of Medicine Medical Subject Headings (MeSH)
- IC50 values for common inhibitors
- "Chemical structures and known kinase targets for clinically approved kinase inhibitors" Nature.com