Southern Research Institute
Encyclopedia
Southern Research Institute is a not-for-profit institute
Research institute
A research institute is an establishment endowed for doing research. Research institutes may specialize in basic research or may be oriented to applied research...

 that conducts basic and applied research sponsored by both commercial and non-commercial organizations in areas such as Drug Discovery
Drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...

, Drug Development
Drug development
Drug development is a blanket term used to define the process of bringing a new drug to the market once a lead compound has been identified through the process of drug discovery...

 and Engineering
Engineering
Engineering is the discipline, art, skill and profession of acquiring and applying scientific, mathematical, economic, social, and practical knowledge, in order to design and build structures, machines, devices, systems, materials and processes that safely realize improvements to the lives of...

 and Environmental Sciences.

History

Southern Research Institute has had a long-standing program in cancer drug discovery. The institute's scientists are credited with the discovery of seven currently used drugs approved by the U.S. 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...

 (FDA) including carmustine
Carmustine
Carmustine or BCNU is a mustard gas-related β-chloro-nitrosourea compound used as an alkylating agent in chemotherapy...

, lomustine
Lomustine
Lomustine is an alkylating nitrosourea compound used in chemotherapy. It is in the same family as streptozotocin. This is a highly lipid soluble drug, and thus crosses the blood brain barrier. This property makes it ideal for treating brain tumors, and is its primary use...

, dacarbazine
Dacarbazine
Dacarbazine is an antineoplastic chemotherapy drug used in the treatment of various cancers, among them malignant melanoma, Hodgkin lymphoma, sarcoma, and islet cell carcinoma of the pancreas.Dacarbazine is a member of the class of alkylating agents, which destroy cancer cells by adding an alkyl...

, fludarabine
Fludarabine
Fludarabine or fludarabine phosphate is a chemotherapy drug used in the treatment of hematological malignancies. It has been unofficially and casually referred to as "AIDS in a bottle" amongst healthcare professionals due to its significant immunosuppresive activity.-Indications:Fludarabine is...

, amifostine
Amifostine
Amifostine is a cytoprotective adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents. It is marketed by MedImmune under the trade name Ethyol.-Indications:...

, clofarabine
Clofarabine
Clofarabine is a purine nucleoside antimetabolite marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra. It is FDA-approved for treating a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia in...

 and the latest pralatrexate (approved in 2009). Notable cancer researchers who worked at the institute include Howard Skipper, John Montgomery, Frank Schabel and Lee Bennett Jr.

Drug Discovery Research

Clofarabine
Clofarabine
Clofarabine is a purine nucleoside antimetabolite marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra. It is FDA-approved for treating a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia in...

 is a nucleoside discovered at Southern Research Institute that eventually received FDA approval. Clofarabine
Clofarabine
Clofarabine is a purine nucleoside antimetabolite marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra. It is FDA-approved for treating a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia in...

, a second-generation nucleoside analogue received accelerated approval from the US FDA at the end of 2004 for the treatment of paediatric patients 1-21 years old with relapsed or refractory acute lymphoblastic leukaemia after at least two prior regimens. It is the first such drug to be approved for paediatric leukaemia in more than a decade, and the first to receive approval for paediatric use before adult use.

Pralatrexate is another anticancer drug whose discovery was a result of contributions from medicinal chemists at Southern Research Institute along with chemists from SRI International
SRI International
SRI International , founded as Stanford Research Institute, is one of the world's largest contract research institutes. Based in Menlo Park, California, the trustees of Stanford University established it in 1946 as a center of innovation to support economic development in the region. It was later...

 and Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
Memorial Sloan–Kettering Cancer Center is a cancer treatment and research institution founded in 1884 as the New York Cancer Hospital...

. The US FDA announced the approval of pralatrexate in 2009 for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL).
. Research on drugs of this class began at SRI International
SRI International
SRI International , founded as Stanford Research Institute, is one of the world's largest contract research institutes. Based in Menlo Park, California, the trustees of Stanford University established it in 1946 as a center of innovation to support economic development in the region. It was later...

 in the 1950s. Pralatrexate was first prepared there by Dr. Joseph DeGraw and Dr. William Colwell. Dr. Robert Piper at Southern Research Institute synthesized the key starting material (a bromomethyl compound) which was used to prepare the intermediates needed to make multigram quantities of high purity final compound. Multiple issued patents on this compound are jointly owned by Southern Research Institute, SRI International
SRI International
SRI International , founded as Stanford Research Institute, is one of the world's largest contract research institutes. Based in Menlo Park, California, the trustees of Stanford University established it in 1946 as a center of innovation to support economic development in the region. It was later...

 and Memorial Sloan Kettering and licensed to Allos Therapeutics.

Molecular Libraries Program (MLP) at Southern Research Institute: Molecular Libraries Screening Centers Network (MLSCN) and Molecular Libraries Production Centers Network (MLPCN)

MLP was founded by the NIH to fund research aimed at identifying new chemical probes against biological targets that might be amenable for drug therapy. Southern Research Institute was one of eight extramural institutes selected for this initiative along with the Broad Institute
Broad Institute
The Broad Institute is a genomic medicine research center located in Cambridge, Massachusetts, United States. Although it is independently governed and supported as a 501 nonprofit research organization, the institute is formally affiliated with the Massachusetts Institute of Technology, Harvard...

, Sanford-Burnham Medical Research Institute, Johns Hopkins University
Johns Hopkins University
The Johns Hopkins University, commonly referred to as Johns Hopkins, JHU, or simply Hopkins, is a private research university based in Baltimore, Maryland, United States...

, Scripps Research Institute, Vanderbilt University
Vanderbilt University
Vanderbilt University is a private research university located in Nashville, Tennessee, United States. Founded in 1873, the university is named for shipping and rail magnate "Commodore" Cornelius Vanderbilt, who provided Vanderbilt its initial $1 million endowment despite having never been to the...

, University of New Mexico
University of New Mexico
The University of New Mexico at Albuquerque is a public research university located in Albuquerque, New Mexico, in the United States. It is the state's flagship research institution...

 and the University of Kansas
University of Kansas
The University of Kansas is a public research university and the largest university in the state of Kansas. KU campuses are located in Lawrence, Wichita, Overland Park, and Kansas City, Kansas with the main campus being located in Lawrence on Mount Oread, the highest point in Lawrence. The...

. In addition the MLP initiative also included an NIH intramural site: the National Center for Chemical Genomics (NCGC).The Molecular Libraries Screening Centers Network (MLSCN) is a national high-throughput biological screening resource that was launched on June 15, 2005. The goals of the MLSCN are to expand the availability and use of chemical probes to explore the function of genes, cells, and pathways in health and disease, and to provide annotated information on the biological activities of compounds contained in the central Molecular Libraries Small Molecule Repository in a public database (PubChem).The workhorse of the MLP program is its 350,000-strong library of unique chemical structures of the NIH’s Molecular Libraries Small Molecule Repository (MLSMR). The MLSMR is screened with biological assays or bioactivity experiments looking for particular areas of biological activity

External links

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