Protein kinase inhibitor
A protein kinase inhibitor is a type of enzyme inhibitor that specifically blocks the action of one or more protein kinases. Hence, they 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.[citation needed]
They can interfere with the repair of DNA double-strand breaks.[1]
Contents |
[edit] Clinical use
Kinase inhibitors such as dasatinib are often used in the treatment of cancer and inflammation.[citation needed] The novel kinase inhibitor PLX5568 is currently in clinical trials for treatment of polycystic kidney disease as well as pain.[2]
Some of the kinase inhibitors used in treating cancer are inhibitors of tyrosine kinases.[3] The effectiveness of kinase inhibitors on various cancers can vary from patient to patient[4].
[edit] Examples
Currently there are several drugs launched or in development that target protein kinases and the receptors that activate them:
| Name | Target | Company | Class | FDA approval |
|---|---|---|---|---|
| Afatinib | EGFR/ErbB2 | Boehringer Ingelheim | Small molecule | Not yet |
| Axitinib | VEGFR1/VEGFR2/VEGFR3/PDGFRB/c-KIT | Pfizer | Small molecule | 2012 Renal cell carcinoma |
| Bevacizumab | VEGF | Genentech | Monoclonal antibody | 2004 Colorectal |
| Cetuximab | Erb1 | 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 | Erb1 | Genentech/Roche | Small molecule | 2005 Nov ? |
| Fostamatinib | Syk | Rigel Pharmaceuticals/AstraZeneca | Small molecule | Not yet [1] |
| Gefitinib | EGFR | AstraZeneca | Small molecule | 2003 |
| Imatinib | Bcr-Abl | Novartis | Small molecule | 2001 (CML) |
| Lapatinib | Erb1/Erb2 | GSK | Small molecule | 2007 (HER2+ Breast) |
| Lenvatinib | VEGFR2/VEGFR2 | Eisai Co. | Small molecule | Not yet |
| Mubritinib | ? | Takeda | Small molecule | Not yet, possibly abandoned |
| Nilotinib | Bcr-Abl | Novartis | Small molecule | 2007 |
| Panitumumab | EGFR | Amgen | Monoclonal antibody | 2006 |
| 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) |
| Trastuzumab | Erb2 | Genentech/Roche | Monoclonal antibody | 1998 (HER2+ breast cancer) |
| Vandetanib | RET/VEGFR/EGFR | AstraZeneca | Small molecule | No, submission withdrawn Oct09 [2] |
| Vemurafenib | BRAF | Roche | Small molecule | 2011 Aug Melanoma |
[edit] See also
[edit] References
- ^ Zhao Y, Thomas HD, Batey MA, et al. (May 2006). "Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441". Cancer Res. 66 (10): 5354–62. doi:10.1158/0008-5472.CAN-05-4275. PMID 16707462. http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16707462.
- ^ "Plexxikon Initiates Phase 1 Trial for PLX5568". http://www.plexxikon.com/pr-090308.html.
- ^ "Definition of tyrosine kinase inhibitor - NCI Dictionary of Cancer Terms". http://www.cancer.gov/templates/db_alpha.aspx?CdrID=44833.
- ^ Factors underlying sensitivity of cancers to small-molecule kinase inhibitors. 8. 2009. http://www.nature.com/nrd/journal/v8/n9/full/nrd2871.html.
[edit] External links
- MeSH Protein+kinase+inhibitors
- IC50 values for common inhibitors
- "Chemical structures and known kinase targets for clinically approved kinase inhibitors" Nature.com
|
|||||||||||||||||||
|
|||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
 |
This biochemistry article is a stub. You can help Wikipedia by expanding it. |
