Protein kinase inhibitor - AbsoluteAstronomy.com

A protein kinase inhibitor is a type of enzyme inhibitor

Enzyme inhibitor

An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...

that specifically blocks the action of one or more protein kinase

Protein kinase

A protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them . Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins...

s. Hence, they can be subdivided or characterised by the amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s whose phosphorylation is inhibited:
most kinases act on both serine and threonine, the tyrosine kinase

Tyrosine kinase

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....

s act on tyrosine, and a number (dual-specificity kinase

Dual-specificity kinase

In biochemistry, a dual-specificity kinase is a kinase that can act as both tyrosine kinase and serine/threonine kinase.MEKs, involved in MAP pathways, are principal examples of dual-specificity kinases...

s) act on all three. There are also protein kinases that phosphorylate other amino acids, including histidine kinase

Histidine kinase

Histidine Kinases are multifunctional, typically transmembrane, proteins of the transferase class that play a role in signal transduction across the cellular membrane. The vast majority of HKs are homodimers that exhibit autokinase, phosphotransfer, and phosphatase activity. HKs can act as...

s that phosphorylate histidine residues.

They can interfere with the repair of DNA double-strand breaks.

Clinical use

Kinase inhibitors such as dasatinib

Dasatinib

Dasatinib, previously known as BMS-354825, is a cancer drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel. Dasatinib is an oral multi- BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia after imatinib treatment...

are often used in the treatment of cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

and inflammation

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

. The novel kinase inhibitor PLX5568 is currently in clinical trials for treatment of polycystic kidney disease

Polycystic kidney disease

Autosomal dominant polycystic kidney disease is an inherited systemic disorder that predominantly affects the kidneys, but may affect other organs including the liver, pancreas, brain, and arterial blood vessels...

as well as pain

Pain

Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...

.

Some of the kinase inhibitors used in treating cancer are inhibitors of tyrosine kinase

Tyrosine kinase

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a protein in a cell. It functions as an "on" or "off" switch in many cellular functions....

s.
The effectiveness of kinase inhibitors on various cancers can vary from patient to patient.

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 Epidermal growth factor receptor The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands... /Erb2	Boehringer Ingelheim	Small molecule Small molecule In the fields of pharmacology and biochemistry, a small molecule is a low molecular weight organic compound which is by definition not a polymer...	>- \| Bevacizumab Bevacizumab Bevacizumab is a drug that blocks angiogenesis, the growth of new blood vessels. It is commonly used to treat various cancers, including colorectal, lung, breast, kidney, and glioblastomas....	VEGF Vascular endothelial growth factor Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....	Genentech Genentech Genentech Inc., or Genetic Engineering Technology, Inc., is a biotechnology corporation, founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert Boyer. Trailing the founding of Cetus by five years, it was an important step in the evolution of the biotechnology industry...	Monoclonal antibody	>- \| Cetuximab Cetuximab Cetuximab is a chimeric monoclonal antibody, an epidermal growth factor receptor inhibitor, given by intravenous infusion for treatment of metastatic colorectal cancer and head and neck cancer.- Distribution :Cetuximab is manufactured and distributed in North America by ImClone and Bristol-Myers...	Erb1 Epidermal growth factor receptor The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...	Imclone/BMS BMS BMS is a three letter acronym that may refer to:* Be-Music Script, a computer file format* Black Mesa * Borane-methylsulfide* Bristol Motor Speedway* Broadmeadows railway station, Melbourne...	Monoclonal antibody	>- \| Crizotinib Crizotinib Crizotinib , is an ALK inhibitor, approved for treatment of some non-small cell lung carcinoma in the US, and undergoing clinical trials testing its safety and efficacy in anaplastic large cell lymphoma, neuroblastoma, and other advanced solid tumors in both adults and children.- Mechanism of...	ALK Anaplastic lymphoma kinase Anaplastic lymphoma kinase also known as ALK tyrosine kinase receptor or CD246 is an enzyme that in humans is encoded by the ALK gene.-Function:... /Met C-MET c-Met is a proto-oncogene that encodes a protein known as hepatocyte growth factor receptor . The hepatocyte growth factor receptor protein possesses tyrosine-kinase activity...	Pfizer Pfizer Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...	Small molecule	>- \| Dasatinib Dasatinib Dasatinib, previously known as BMS-354825, is a cancer drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel. Dasatinib is an oral multi- BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia after imatinib treatment...	multiple targets	BMS BMS BMS is a three letter acronym that may refer to:* Be-Music Script, a computer file format* Black Mesa * Borane-methylsulfide* Bristol Motor Speedway* Broadmeadows railway station, Melbourne...	Small molecule	>- \| Erlotinib Erlotinib Erlotinib hydrochloride is a drug used to treat non-small cell lung cancer, pancreatic cancer and several other types of cancer. It is a reversible tyrosine kinase inhibitor, which acts on the epidermal growth factor receptor . It is marketed in the United States by Genentech and OSI...	Erb1 ERB1 Erb1 also known as the eukaryotic ribosome biogenesis protein 1 is a yeast protein required for maturation of the 25S and 5.8S ribosomal RNAs. It is a component of 66S pre-ribosomal particles and is homologous to the human protein BOP1....	Genentech Genentech Genentech Inc., or Genetic Engineering Technology, Inc., is a biotechnology corporation, founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert Boyer. Trailing the founding of Cetus by five years, it was an important step in the evolution of the biotechnology industry... /Roche	Small molecule	>- \| Fostamatinib Fostamatinib Fostamatinib is an experimental drug candidate for the treatment of a variety of diseases. It is in Phase III clinical trials for rheumatoid arthritis and Phase II trials for autoimmune thrombocytopenia and...	Syk Syk Spleen tyrosine kinase, also known as Syk, is an enyzme which in humans is encoded by the SYK gene.- Function :SYK, along with Zap-70, is a member of the Syk family of tyrosine kinases...	Rigel Pharmaceuticals/AstraZeneca AstraZeneca AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...	Small molecule	http://www.ncbi.nlm.nih.gov/pubmed/19333898 >- \| Gefitinib Gefitinib Gefitinib INN , trade name Iressa, is a drug used in the treatment of certain types of cancer, particularly those with mutated and overactive EGFR. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor in target cells...	EGFR Epidermal growth factor receptor The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...	AstraZeneca AstraZeneca AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...	Small molecule	>- \| Imatinib Imatinib Imatinib is a drug used to treat certain types of cancer. It is currently marketed by Novartis as Gleevec or Glivec as its mesylate salt, imatinib mesilate . It is used in treating chronic myelogenous leukemia , gastrointestinal stromal tumors and some other diseases...	Bcr-Abl	Novartis Novartis Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...	Small molecule	>- \| Lapatinib Lapatinib Lapatinib , used in the form of lapatinib ditosylate, is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2 growth receptor pathway. It is used in combination therapy for HER2-positive breast cancer...	Erb1 ERB1 Erb1 also known as the eukaryotic ribosome biogenesis protein 1 is a yeast protein required for maturation of the 25S and 5.8S ribosomal RNAs. It is a component of 66S pre-ribosomal particles and is homologous to the human protein BOP1.... /Erb2	GSK GSK GSK could refer to:* Get Started Kit * GlaxoSmithKline , a multinational pharmaceutical corporation* Global Security Kit, a cryptographic programming library by IBM* GSK-3, a protein kinase...	Small molecule	>- \| Lenvatinib	VEGFR2/VEGFR2	Eisai Co. Eisai Co. is a Japanese pharmaceutical company, ranking among the top 25 in the world by revenue and achieving $8 billion USD in sales for the fiscal 2008 year. Headquartered in Tokyo, Japan, it has some 10,000 employees, among them about 1,500 in research. Eisai is a member of the Topix 100 and Nikkei 225...	Small molecule	>- \| Mubritinib Mubritinib Mubritinib is a protein kinase inhibitor which was under development by Takeda for the treatment of cancer. It completed phase I clinical trials but appears to have been discontinued, as no new information on the drug has surfaced since December 2008.- References :...	?	Takeda Takeda Pharmaceutical Company is the largest pharmaceutical company in Japan and Asia and a top 15 pharmaceutical company. The company has over 19,000 employees worldwide and achieved $15.7 billion USD in revenue during the 2008 fiscal year...	Small molecule	>- \| Nilotinib Nilotinib Nilotinib , in the form of the hydrochloride monohydrate salt, is a tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia.-Uses:...	Bcr-Abl	Novartis Novartis Novartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...	Small molecule	>- \| Panitumumab Panitumumab Panitumumab , formerly ABX-EGF, is a fully human monoclonal antibody specific to the epidermal growth factor receptor ....	EGFR Epidermal growth factor receptor The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...	Amgen Amgen Amgen Inc. is an international biotechnology company headquartered in Thousand Oaks, California. Located in the Conejo Valley, Amgen is the world's largest independent biotech firm. The company employs approximately 17,000 staff members. Its products include Epogen, Aranesp, Enbrel, Kineret,...	Monoclonal antibody	>- \| Pazopanib Pazopanib Pazopanib is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit that blocks tumor growth and inhibits angiogenesis. It has been approved for renal cell carcinoma by the U.S. Food and Drug Administration. Pazopanib may also be...	VEGFR2/PDGFR/c-kit	GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...	Small molecule	>- \| Pegaptanib Pegaptanib Pegaptanib sodium injection is an anti-angiogenic medicine for the treatment of neovascular age-related macular degeneration . It was discovered by Gilead Sciences and licensed in 2000 to EyeTech Pharmaceuticals, now OSI Pharmaceuticals, for late stage development and marketing in the United...	VEGF Vascular endothelial growth factor Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....	OSI OSI - General :* OSI Pharmaceuticals, an American pharmaceutical company* OSI Restaurant Partners, the restaurant and entertainment group that includes Outback Steakhouse... /Pfizer Pfizer Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...	RNA Aptamer Aptamer Aptamers are oligonucleic acid or peptide molecules that bind to a specific target molecule. Aptamers are usually created by selecting them from a large random sequence pool, but natural aptamers also exist in riboswitches. Aptamers can be used for both basic research and clinical purposes as...	>- \| Ranibizumab Ranibizumab Ranibizumab is a monoclonal antibody fragment derived from the same parent mouse antibody as bevacizumab . It is much smaller than the parent molecule and has been affinity matured to provide stronger binding to VEGF-A...	VEGF Vascular endothelial growth factor Vascular endothelial growth factor is a signal protein produced by cells that stimulates vasculogenesis and angiogenesis. It is part of the system that restores the oxygen supply to tissues when blood circulation is inadequate....	Genentech Genentech Genentech Inc., or Genetic Engineering Technology, Inc., is a biotechnology corporation, founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert Boyer. Trailing the founding of Cetus by five years, it was an important step in the evolution of the biotechnology industry...	Monoclonal antibody	>- \| Ruxolitinib	JAK Janus kinase Janus kinase is a family of intracellular, non-receptor tyrosine kinases that transduce cytokine-mediated signals via the JAK-STAT pathway. They were initially named "just another kinase" 1 & 2 , but were ultimately published as "Janus kinase"...	Incyte	Small molecule	>- \| Sorafenib Sorafenib Sorafenib , is a drug approved for the treatment of primary kidney cancer and advanced primary liver cancer ....	multiple targets	Onyx Onyx Onyx is a banded variety of chalcedony. The colors of its bands range from white to almost every color . Commonly, specimens of onyx contain bands of black and/or white.-Etymology:... /Bayer Bayer Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...	Small molecule	>- \| Sunitinib Sunitinib Sunitinib is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor that was approved by the FDA for the treatment of renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor on January 26, 2006...	multiple targets	SUGEN SUGEN SUGEN was a drug discovery company focused on development of protein kinase inhibitors. It was founded in 1991, and shut down in 2003, after pioneering protein kinases as therapeutic targets and developing the successful cancer therapy sunitinib .-Early history and focus:Sugen was founded in 1991... /Pfizer Pfizer Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...	Small molecule	>- \| Trastuzumab Trastuzumab Trastuzumab is a monoclonal antibody that interferes with the HER2/neu receptor.The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell to inside the cell, and turn genes on and off...	Erb2	Genentech Genentech Genentech Inc., or Genetic Engineering Technology, Inc., is a biotechnology corporation, founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert Boyer. Trailing the founding of Cetus by five years, it was an important step in the evolution of the biotechnology industry... /Roche	Monoclonal antibody	>- \| Vandetanib Vandetanib Vandetanib , also known as ZD6474, is an antagonist of the vascular endothelial growth factor receptor and the epidermal growth factor receptor ....	RET RET proto-oncogene The RET proto-oncogene encodes a receptor tyrosine kinase for members of the glial cell line-derived neurotrophic factor family of extracellular signalling molecules.... /VEGFR/EGFR Epidermal growth factor receptor The epidermal growth factor receptor is the cell-surface receptor for members of the epidermal growth factor family of extracellular protein ligands...	AstraZeneca AstraZeneca AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...	Small molecule	http://www.astrazeneca.com/media/latest-press-releases/zactima-adv-NSCLC?itemId=7317146 >- \| Vemurafenib	BRAF BRAF BRAF can refer to* Baton Rouge Area Foundation* The BRAF gene...	Roche Roche Roche is French for "boulder/rock". The word is several names:-Business & companies:* Hoffmann–La Roche AG, Basel, Switzerland, one of the largest pharmaceutical companies in the world....	Small molecule	2011 Aug (Melanoma)

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