SUGEN
Encyclopedia
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).
, 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 been credited with pioneering this area http://jnci.oxfordjournals.org/content/95/14/1036.full Research Retreat: Pfizer Eliminates Sugen, Shrinks Cancer Infrastructure (subscription required)., leading to protein kinases being the second most active area of drug development, largely based on ATP-competitive inhibitors. Sugen also had research programs on protein phosphatases, none of which lead to therapeutics.
(IND) application, for a PDGFR inhibitor, SU101 . This failed clinically, but was followed by a different series of compounds that inhibited VEGFR kinases (involved in angiogenesis) as well as PDGFR and Kit. Of these, SU5416 (Semaxanib
) and SU6668 went into clinical trials for colon cancer in 1999. SU5416 proceeded to Phase 3 trials, while the follow-on compound, SU11248 (Sunitinib
) was later approved for human use, and a related compound SU11654 (Toceranib
) was approved for canine tumors.
Sugen was funded though a number of collaborative research programs with companies including ASTA Medica (pan-Her and Raf programs), Allergan (opthalmic angiogenesis inhibition), Zeneca (EGFR and cancer), and Amgen all of which took equity stakes in the company , and Taiho (cancer) . Conversely, Sugen was an investor in and collaborator with Selectide for the development of peptide kinase inhibitors.
). Pharmacia was then acquired by Pfizer
in 2002-3 .
) , leading to Food and Drug Administration
approval in January 2006 for treatment of RCC and GIST tumors. Other programs also transferred to Pfizer, including a follow-on compound to SU11248, known as SU14813, and programs on Met and PAK kinases. Work started at Sugen also contributed to the development of the ALK inhibitor crizotinib
(Xalkori), FDA-approved for NSCLC in 2011. Sugen also generated extensive basic research on kinase biology, including the publication of almost 300 research papers , the definition of the human kinome
, and the discovery of over 140 human kinase genes. Sugen alumni have gone on to major positions in other pharmaceutical and kinase-focused companies. In 2010, Sutent surpassed $1bn in annual revenues for Pfizer. and as of May 2011, over 100,000 patients had been treated with Sutent.
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...
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
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...
(Sutent).
Early history and focus
Sugen was founded in 1991 in Redwood CityRedwood City, California
Redwood City is a California charter city located on the San Francisco Peninsula in Northern California, approximately 27 miles south of San Francisco, and 24 miles north of San Jose. Redwood City's history spans from its earliest inhabitation by the Ohlone people, to its tradition as a port for...
, California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...
, by veteran biotech investor Stephen Evans-Freke and kinase researchers Joseph Schlessinger
Joseph Schlessinger
Joseph "Josip" Schlessinger is a Croatian-born Israeli 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...
and Axel Ullrich
Axel Ullrich
Axel Ullrich in is a German cancer researcher and has been the Director of the Molecular biology dept. at the Max Planck Institute of Biochemistry in Martinsried, Germany since 1988. This deptartment's research has primarily focused on signal transduction...
. 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
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
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
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
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 been credited with pioneering this area http://jnci.oxfordjournals.org/content/95/14/1036.full Research Retreat: Pfizer Eliminates Sugen, Shrinks Cancer Infrastructure (subscription required)., leading to protein kinases being the second most active area of drug development, largely based on ATP-competitive inhibitors. Sugen also had research programs on protein phosphatases, none of which lead to therapeutics.
Research and drug development
Sugen went public in October 1994 (NASDAQ: SUGN), and shortly after filed its first Investigational New DrugInvestigational New Drug
The United States Food and Drug Administration's Investigational New Drug program is the means by which a pharmaceutical company obtains permission to ship an experimental drug across state lines before a marketing application for the drug has been approved...
(IND) application, for a PDGFR inhibitor, SU101 . This failed clinically, but was followed by a different series of compounds that inhibited VEGFR kinases (involved in angiogenesis) as well as PDGFR and Kit. Of these, SU5416 (Semaxanib
Semaxanib
Semaxanib 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 of clinical trials....
) and SU6668 went into clinical trials for colon cancer in 1999. SU5416 proceeded to Phase 3 trials, while the follow-on compound, SU11248 (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...
) was later approved for human use, and a related compound SU11654 (Toceranib
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 , Toceranib is the only dog-specific anti-cancer drug approved by the U.S. Food and Drug Administration. It is marketed as Palladia as its...
) was approved for canine tumors.
Sugen was funded though a number of collaborative research programs with companies including ASTA Medica (pan-Her and Raf programs), Allergan (opthalmic angiogenesis inhibition), Zeneca (EGFR and cancer), and Amgen all of which took equity stakes in the company , and Taiho (cancer) . Conversely, Sugen was an investor in and collaborator with Selectide for the development of peptide kinase inhibitors.
Mergers
Sugen was acquired by Pharmaica & Upjohn in 1999 in a stock swap valued at $650 million, and run in a largely autonomous manner through several other mergers and splits at the parent company (later renamed PharmaciaPharmacia
Pharmacia was a pharmaceutical and biotechnological company in Sweden.-History:Pharmacia 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'...
). Pharmacia was then acquired by 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...
in 2002-3 .
Shutdown and legacy
The Pfizer-Pharmacia merger lead to major cuts in research activities, including the shut down of Sugen over the course of 2003, with the loss of approximately 350 employees. Pfizer continued the phase 3 trials and development of SU11248, now known as Sutent (sunitinibSunitinib
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...
) , leading to Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
approval in January 2006 for treatment of RCC and GIST tumors. Other programs also transferred to Pfizer, including a follow-on compound to SU11248, known as SU14813, and programs on Met and PAK kinases. Work started at Sugen also contributed to the development of the ALK inhibitor 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...
(Xalkori), FDA-approved for NSCLC in 2011. Sugen also generated extensive basic research on kinase biology, including the publication of almost 300 research papers , the definition of the human kinome
Kinome
In molecular biology, the kinome of an organism is the set of protein kinases in its genome. Kinases are enzymes that catalyze phosphorylation reactions and fall into several groups and families, e.g., those that phosphorylate the amino acids serine and threonine, those that phosphorylate tyrosine...
, and the discovery of over 140 human kinase genes. Sugen alumni have gone on to major positions in other pharmaceutical and kinase-focused companies. In 2010, Sutent surpassed $1bn in annual revenues for Pfizer. and as of May 2011, over 100,000 patients had been treated with Sutent.