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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 (Sutent). Early history and focus Sugen was founded in 1991 in Redwood City, California, by veteran biotech investor Stephen Evans-Freke and kinase researchers Joseph Schlessinger and Axel Ullrich. The name was derived from the initials of Schlessinger and Ullrich, and the "GEN" for Genetics. Sugen developed small-molecule inhibitors of protein kinases, key enzymes in signal transduction and cellular decision-making. The main focus was on oncology, though the company had collaborations in other therapeutic areas. The concept of inhibiting kinases by small molecules that mimicked the ATP structure was generally thought to be infeasible when the company was founded (due to the high (mM) concentration of ATP in cells), and Sugen has ...
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Pfizer
Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer (1824–1906) and his cousin Charles F. Erhart (1821–1891). Pfizer develops and produces medicines and vaccines for immunology, oncology, cardiology, endocrinology, and neurology. The company has several blockbuster drugs or products that each generate more than billion in annual revenues. In 2020, 52% of the company's revenues came from the United States, 6% came from each of China and Japan, and 36% came from other countries. Pfizer was a component of the Dow Jones Industrial Average stock market index from 2004 to August 2020. The company ranks 64th on the Fortune 500 and 49th on the Forbes Global 2000. History 1849–1950: Early history Pfizer was founded in 1849 by Charles Pfizer and Charles F. Erhart, two cousins who had i ...
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Axel Ullrich
Axel Ullrich (born 19 October 1943) is a German cancer researcher and has been the director of the molecular biology department at the Max Planck Institute of Biochemistry in Martinsried, Germany since 1988. This department's research has primarily focused on signal transduction. Ullrich has received Hamdan Award for Medical Research Excellence, awarded by Sheikh Hamdan bin Rashid Al Maktoum Award for Medical Sciences, Dubai, United Arab Emirates in 2008 and Ullrich and his team received the Wolf Prize in 2010. Life and work Ullrich received his primary degree in biochemistry at the University of Tübingen, Germany, he received a Ph.D. from the University of Heidelberg in Molecular Genetics in 1975. He did post-doctoral work at the University of California, San Francisco, from 1975 to 1977 and worked as a senior scientist at Genentech in San Francisco from 1978 to 1988. From 1988, he has been at the Max Planck Institute of Biochemistry. Ullrich was the first person to clone a hu ...
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Joseph Schlessinger
Joseph Schlessinger (born Josip Schlessinger; 26 March 1945) is a Yugoslav-born Israeli- American biochemist and biophysician. He is chair of the Pharmacology Department at Yale University School of Medicine in New Haven, Connecticut, as well as the founding director of the school's new Cancer Biology Institute. His area of research is signaling through tyrosine phosphorylation, which is important in many areas of cellular regulation, especially growth control and cancer. Schlessinger's work has led to an understanding of the mechanism of transmembrane signaling by receptor tyrosine kinases and how the resulting signals control cell growth and differentiation. Biography Josip Schlessinger was born in Topusko to Jewish parents. His father, Imre, was from Slatina; Imre's first wife and child had been deported to Auschwitz. Schlessinger's mother Rivka was from Bugojno; her first husband had been murdered by the Ustaše. Imre and Rivka met in a labor camp in 1943 on the Adr ...
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Semaxanib
Semaxanib (SU5416) is a tyrosine-kinase inhibitor drug designed by SUGEN as a cancer therapeutic. It is an experimental stage drug, not licensed for use on human patients outside clinical trials. Semaxanib is a potent and selective synthetic inhibitor of the Flk-1/KDR vascular endothelial growth factor (VEGF) receptor tyrosine kinase. It targets the VEGF pathway, and both ''in vivo'' and ''in vitro'' studies have demonstrated antiangiogenic potential. In February 2002, Pharmacia, the then-parent of Sugen, prematurely ended Phase III clinical trials of semaxinib in the treatment of advanced colorectal cancer due to discouraging results. Other studies, at earlier phases, have since been conducted. However, due to the prospect of next-generation tyrosine kinase inhibitors and the inefficacy of semaxanib in clinic trials, further development of the drug has been discontinued. A related compound, SU11248 was further developed by Sugen, and then by Pfizer Pfizer Inc. ( ) i ...
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Toceranib
Toceranib is a receptor tyrosine kinase inhibitor and is used in the treatment of canine mast cell tumor also called mastocytoma. Together with masitinib (Kinavet (US)/Masivet (EU/ROW) by AB Science), toceranib is the only dog-specific anti-cancer drug approved by the U.S. Food and Drug Administration (FDA). It is sold under the brand name Palladia as its phosphate salt, toceranib phosphate (INN) by Pfizer Pfizer Inc. ( ) is an American multinational pharmaceutical and biotechnology corporation headquartered on 42nd Street in Manhattan, New York City. The company was established in 1849 in New York by two German entrepreneurs, Charles Pfizer .... It was developed by SUGEN as SU11654, a sister compound to sunitinib, which was later approved for human therapies. Toceranib is likely to act mostly through inhibition of the kit tyrosine kinase, though it may also have an anti-angiogenic effect. References External links * Receptor tyrosine kinase inhibitors Fluo ...
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Sunitinib
Sunitinib, sold under the brand name Sutent, is a medication used to treat cancer. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications. As of August 2021, sunitinib is available as a generic medicine in the US. Medical uses Gastrointestinal stromal tumor Like RCC, GIST does not generally respond to standard chemotherapy or radiation. Imatinib was the first cancer agent proven effective for metastatic GIST and represented a major development in the treatment of this rare but challenging disease. However, approximately 20% of patients do not respond to imatinib (early or primary resistance), and among those who do respond initially, 50% develop secondary imatinib resistance and disease progression within t ...
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Sunitinib
Sunitinib, sold under the brand name Sutent, is a medication used to treat cancer. It is a small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications. As of August 2021, sunitinib is available as a generic medicine in the US. Medical uses Gastrointestinal stromal tumor Like RCC, GIST does not generally respond to standard chemotherapy or radiation. Imatinib was the first cancer agent proven effective for metastatic GIST and represented a major development in the treatment of this rare but challenging disease. However, approximately 20% of patients do not respond to imatinib (early or primary resistance), and among those who do respond initially, 50% develop secondary imatinib resistance and disease progression within t ...
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Protein Kinase
A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein ( substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase. The great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets and most of the others are tyrosine kinases, although additional types exist. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction. Chemical ac ...
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Kinome
In molecular biology, biochemistry and cell signaling the kinome of an organism is the complete set of protein kinases encoded in its genome. Kinases are usually enzymes that catalyze phosphorylation reactions (of amino acids) and fall into several groups and families, e.g., those that phosphorylate the amino acids serine and threonine, those that phosphorylate tyrosine and some that can phosphorylate both, such as the MAP2K and GSK families. The term was first used in 2002 by Gerard Manning and colleagues in twin papers analyzing the 518 human protein kinases, and refers to both protein kinases and protein pseudokinases and their evolution of protein kinases throughout the eukaryotes. Other kinomes have been determined for rice, several fungi, nematodes, and insects, sea urchins, ''Dictyostelium discoideum'', and the process of infection by ''Mycobacterium tuberculosis''. Although the primary sequence of protein kinases shows substantial divergence between unrelated eukaryotes, and ...
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Crizotinib
Crizotinib, sold under the brand name Xalkori among others, is an anti-cancer medication used for the treatment of non-small cell lung carcinoma (NSCLC). It acts as an ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene 1) inhibitor. Medical uses Crizotinib is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) or relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive. It is also indicated for the treatment of unresectable, recurrent, or refractory inflammatory anaplastic lymphoma kinase (ALK)-positive myofibroblastic tumors (IMT). Mechanism of action Crizotinib has an aminopyridine structure, and functions as a protein kinase inhibitor by competitive binding within the Adenosine triphosphate, ATP-binding pocket of target kinases. About 4% of patients with non-small cell lung carcinoma have a chromosome, chromosomal rearrangement that generates a fusion gene between ''EML4'' ('echinoderm microtubule-associ ...
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Food And Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, caffeine products, dietary supplements, Prescription drug, prescription and Over-the-counter drug, over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, Animal feed, animal foods & feed and Veterinary medicine, veterinary products. The FDA's primary focus is enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C), but the agency also enforces other laws, notably Section 361 of the Public Health Service Act, as well as associated regulations. Much of this regulatory-enforcement work is not d ...
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Pharmacia
Pharmacia was a pharmaceutical and biotechnological company in Sweden that merged with the American pharmaceutical company Upjohn in 1995. History Pharmacia company was founded in 1911 in Stockholm, Sweden by pharmacist Gustav Felix Grönfeldt at the ''Elgen'' Pharmacy. The company is named after the Greek word φαρμακεία, transliterated ''pharmakeia'', which means 'sorcery'. In the company's early days, much of its profits were derived from the "miracle medicine" Phospho-Energon. During World War II, Swedish chemist Björn Ingelman (who worked for Arne Tiselius at Uppsala university) researched various uses for the polysaccharide dextran. Together with the medical researcher Anders Grönwall, he discovered that dextran could be used as a replacement for blood plasma in blood transfusions, for which there could be a large need in wartime. Pharmacia, which then was still a small company, was contacted in 1943 and its CEO Elis Göth was very interested. The product Macrod ...
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