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| Established | 2006 |
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| Research type | Unclassified/classified |
| Director | Robert Roskoski Jr. |
| Location | Horse Shoe, North Carolina, U.S. |
| Website | brimr |
The Blue Ridge Institute for Medical Research (BRIMR) is an independent, non-profit, scientific research institute located in Horse Shoe, North Carolina. [1] [2] The Institute was founded by Robert Roskoski Jr., who serves as President and Scientific Director.
The general goals of the Institute are to explore the interrelationships of fundamental biological science, clinical science, and clinical care. [3]
Research at BRIMR focuses on the structure and regulation of protein kinases, their downstream signaling pathways, and therapeutic drugs that inhibit these enzymes. [4] Protein kinases regulate the activity of their substrate targets by adding phosphate groups in a reaction known as protein phosphorylation. [5] The United States Food and Drug Administration has approved the use of about 50 protein kinase inhibitors for the treatment of several cancers including those of breast, kidney, and lung and inflammatory diseases such as rheumatoid arthritis and ulcerative colitis. [6] [7] An average of two to three new drugs of this type is approved annually.
An important component of the Institute's fundamental research involves the study of the nature of the interaction of these anticancer and anti-inflammatory agents with their target protein kinase enzyme. Institute studies are based upon the X-ray crystallographic results that are in the public domain as well as in-house computer-generated models of drugs binding to their targets. [8] The Institute functions as a scientific think tank and performs no actual laboratory work. However, the Institute uses results from the research areas of biochemistry and molecular, chemical, structural and cancer biology in an effort to understand the mechanisms of action of protein kinase inhibitors and the aberrations that result in neoplastic growth.
The results of these studies have been published. [9]
The Blue Ridge Institute for Medical Research has monitored NIH funding to Medical Schools as well as other health science schools and organizations since 2006. [10] BRIMR generates an annual ranking of NIH funding for US Medical Schools and their Departments [11] and the BRIMR data is considered to be the gold standard for medical school research metrics. [12] These data are used throughout the biomedical community for the analysis of medical research and educational activities [13] [14] [15] [16]
Imatinib, sold under the brand names Gleevec and Glivec (both marketed worldwide by Novartis) among others, is an oral chemotherapy medication used to treat cancer. Imatinib is a small molecule inhibitor targeting multiple receptor tyrosine kinases such as CSF1R, ABL, c-KIT, FLT3, and PDGFR-β. Specifically, it is used for chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL) that are Philadelphia chromosome-positive (Ph+), certain types of gastrointestinal stromal tumors (GIST), hypereosinophilic syndrome (HES), chronic eosinophilic leukemia (CEL), systemic mastocytosis, and myelodysplastic syndrome.
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered.
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
Lopinavir is an antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir (lopinavir/ritonavir).
An enzyme inhibitor is a molecule that binds to an enzyme and blocks its activity. Enzymes are proteins that speed up chemical reactions necessary for life, in which substrate molecules are converted into products. An enzyme facilitates a specific chemical reaction by binding the substrate to its active site, a specialized area on the enzyme that accelerates the most difficult step of the reaction.
The Structural Genomics Consortium (SGC) is a public-private-partnership focusing on elucidating the functions and disease relevance of all proteins encoded by the human genome, with an emphasis on those that are relatively understudied. The SGC places all its research output into the public domain without restriction and does not file for patents and continues to promote open science. Two recent publications revisit the case for open science. Founded in 2003, and modelled after the Single Nucleotide Polymorphism Database (dbSNP) Consortium, the SGC is a charitable company whose Members comprise organizations that contribute over $5,4M Euros to the SGC over a five-year period. The Board has one representative from each Member and an independent Chair, who serves one 5-year term. The current Chair is Anke Müller-Fahrnow (Germany), and previous Chairs have been Michael Morgan (U.K.), Wayne Hendrickson (U.S.A.), Markus Gruetter (Switzerland) and Tetsuyuki Maruyama (Japan). The founding and current CEO is Aled Edwards (Canada). The founding Members of the SGC Company were the Canadian Institutes of Health Research, Genome Canada, the Ontario Research Fund, GlaxoSmithKline and Wellcome Trust. The current Members comprise Bayer Pharma AG, Bristol Myers Squibb, Boehringer Ingelheim, the Eshelman Institute for Innovation, Genentech, Genome Canada, Janssen, Merck KGaA, Pfizer, and Takeda.
Nilotinib, sold under the brand name Tasigna marketed worldwide by Novartis, is a medication used to treat chronic myelogenous leukemia (CML) which has the Philadelphia chromosome. It may be used both in initial cases of chronic phase CML as well as in accelerated and chronic phase CML that has not responded to imatinib. It is taken by mouth.
Dasatinib, sold under the brand name Sprycel among others, is a targeted therapy medication used to treat certain cases of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Specifically it is used to treat cases that are Philadelphia chromosome-positive (Ph+). It is taken by mouth.
G-protein-coupled receptor kinase 2 (GRK2) is an enzyme that in humans is encoded by the ADRBK1 gene. GRK2 was initially called Beta-adrenergic receptor kinase, and is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases that is most highly similar to GRK3(βARK2).
A protein kinase inhibitor is a type of enzyme inhibitor that blocks the action of one or more protein kinases. Protein kinases are enzymes that phosphorylate (add a phosphate, or PO4, group) to a protein and can modulate its function.
Cluster of differentiation antigen 135 (CD135) also known as fms like tyrosine kinase 3 (FLT-3), receptor-type tyrosine-protein kinase FLT3, or fetal liver kinase-2 (Flk2) is a protein that in humans is encoded by the FLT3 gene. FLT3 is a cytokine receptor which belongs to the receptor tyrosine kinase class III. CD135 is the receptor for the cytokine Flt3 ligand (FLT3L).
A CDK inhibitor is any chemical that inhibits the function of CDKs. They are used to treat cancers by preventing overproliferation of cancer cells. The US FDA approved the first drug of this type, palbociclib (Ibrance), a CDK4/6 inhibitor, in February 2015, for use in postmenopausal women with breast cancer that is estrogen receptor positive and HER2 negative. Several compounds are in clinical trials.
c-Met inhibitors are a class of small molecules that inhibit the enzymatic activity of the c-Met tyrosine kinase, the receptor of hepatocyte growth factor/scatter factor (HGF/SF). These inhibitors may have therapeutic application in the treatment of various types of cancers.
mTOR inhibitors are a class of drugs that inhibit the mechanistic target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). mTOR regulates cellular metabolism, growth, and proliferation by forming and signaling through two protein complexes, mTORC1 and mTORC2. The most established mTOR inhibitors are so-called rapalogs, which have shown tumor responses in clinical trials against various tumor types.
Pexidartinib, sold under the brand name Turalio, is a kinase inhibitor drug for the treatment of adults with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Pexidartinib blocks the activity of the colony-stimulating factor-1 receptor (CSF-1R).
Entrectinib, sold under the brand name Rozlytrek, is an anti-cancer medication used to treat ROS1-positive non-small cell lung cancer and NTRK fusion-positive solid tumors. It is a selective tyrosine kinase inhibitor (TKI), of the tropomyosin receptor kinases (TRK) A, B and C, C-ros oncogene 1 (ROS1) and anaplastic lymphoma kinase (ALK).
Craig M. Crews is an American scientist at Yale University. He is the John C. Malone Professor of Molecular, Cellular, and Developmental Biology, and also holds joint appointments in the departments of Chemistry and Pharmacology. Crews is the Executive Director of the Yale Center for Molecular Discovery and a former Editor of the journal Cell Chemical Biology. His research interests focus on chemical biology, particularly on controlled proteostasis. Crews is a pioneer in the field of targeted protein degradation and his lab's research led to the development of the anti-cancer drug carfilzomib (Kyprolis). He is the founder of Arvinas, the first biotechnology company to bring PROTAC drugs into clinical trials. In 2019, he was named an American Cancer Society Research Professor at the Yale University.
Poziotinib is a drug in development by Hanmi Pharmaceutical, Luye Pharma (China), and Spectrum Pharmaceuticals for various cancers.
Pemigatinib, sold under the brand name Pemazyre, is an anti-cancer medication used for the treatment of bile duct cancer (cholangiocarcinoma). Pemigatinib works by blocking FGFR2 in tumor cells to prevent them from growing and spreading.
Robert Roskoski Jr. is the Scientific Director and President of the Blue Ridge Institute for Medical Research.
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