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SUGEN (Sugen) was a drug discovery company focused on development of
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 fu ...
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, 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 i ...
(Sutent).


Early history and focus

Sugen was founded in 1991 in
Redwood City Redwood City is a city on the San Francisco Peninsula in Northern California's Bay Area, approximately south of San Francisco, and northwest of San Jose. Redwood City's history spans its earliest inhabitation by the Ohlone people to being a po ...
,
California California is a U.S. state, state in the Western United States, located along the West Coast of the United States, Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the List of states and territori ...
, by veteran biotech investor Stephen Evans-Freke and kinase researchers
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 wel ...
and
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 primar ...
. 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 is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
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, 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 led to therapeutics.


Research and drug development

Sugen went public in October 1994 (NASDAQ: SUGN). In 1997, it filed its first Investigational New Drug (IND) application, for a PDGFR inhibitor, SU101. This failed clinically, but was followed by a different series of compounds that inhibited
VEGFR VEGF receptors are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Also, they may be membrane-bound (mbVEGFR) or soluble (sVEGFR), depending on alternative splicing. Inh ...
kinases (involved in angiogenesis) as well as
PDGFR Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellu ...
and Kit. Of these, SU5416 (
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 i ...
) 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, 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 i ...
) was later approved for human use, and a related compound SU11654 (
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-canc ...
) was approved for canine tumors. Sugen was funded through a number of collaborative research programs with companies including ASTA Medica (pan-Her and Raf programs), Allergan (ophthalmic 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
Pharmacia & Upjohn Pharmacia & Upjohn was a global pharmaceutical company formed by the merger of Sweden-based Pharmacia AB and the American company The Upjohn Company, Upjohn in 1995. Today the remainder of the company is owned by Pfizer. In 1997, Pharmacia & Upjo ...
in 1999 in a stock swap valued at $650 million. In December 1999, Pharmacia & Upjohn merged with
Monsanto The Monsanto Company () was an American agrochemical and agricultural biotechnology corporation founded in 1901 and headquartered in Creve Coeur, Missouri. Monsanto's best known product is Roundup, a glyphosate-based herbicide, developed in th ...
. The company was renamed
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 ...
in 2002. Pharmacia was then acquired 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 ...
in April 2003.


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 (
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 i ...
), leading to
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 respon ...
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, 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. Med ...
(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 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 severa ...
, 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.


References

{{Pharmaceutical companies of the United States Pharmaceutical companies of the United States Health care companies based in California