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Craig M. Crews
Craig M. Crews (born June 1, 1964) 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. Education and training Crews graduated from the University of Virginia in 1986 with a bachelor's degree in chemistry, after which he performed research at the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chemical Biology
Chemical biology is a scientific discipline spanning the fields of chemistry and biology. The discipline involves the application of chemical techniques, analysis, and often small molecules produced through synthetic chemistry, to the study and manipulation of biological systems. In contrast to biochemistry, which involves the study of the chemistry of biomolecules and regulation of biochemical pathways within and between cells, chemical biology deals with chemistry ''applied to'' biology (synthesis of biomolecules, the simulation of biological systems, etc.). Introduction Some forms of chemical biology attempt to answer biological questions by studying biological systems at the chemical level. In contrast to research using biochemistry, genetics, or molecular biology, where mutagenesis can provide a new version of the organism, cell, or biomolecule of interest, chemical biology probes systems ''in vitro'' and ''in vivo'' with small molecules that have been designed for a specific ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carfilzomib
Carfilzomib, sold under the brand name Kyprolis, is an anti-cancer medication acting as a selective proteasome inhibitor. Chemically, it is a tetrapeptide epoxyketone and an analog of epoxomicin. It was developed by Onyx Pharmaceuticals. The U.S. Food and Drug Administration (FDA) approved it on 20 July 2012, for use in people with multiple myeloma who have received at least two prior therapies, including treatment with bortezomib and an immunomodulatory therapy (such as lenalidomide) and have demonstrated disease progression on or within 60 days of completion of the last therapy. Initial approval was based on response rate. Data demonstrating an Overall Survival (OS) benefit was later demonstrated in the ENDEAVOR trial and approved by the FDA.FDA Approves Carfilzomib Label Update in Myeloma , OncLive The abbreviation CFZ is common for referring to carfilzomib, but abbreviating drug names is not best practice in medicine. History Carfilzomib is derived from epoxomicin, a n ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Onyx Pharmaceuticals
Onyx Pharmaceuticals Inc. has been a biopharmaceutical company headquartered in South San Francisco, California. The company developed and marketed medicines for the treatment of cancer. Onyx was founded in 1992 by Kevin J. Kinsella and Frank McCormick Ph.D., FRS. McCormick served as the chief scientific officer until 1998, while Kinsella was the firm's chairman. In 2009, the company acquired Proteolix, Inc., a private biotechnology company, for $276 million in cash plus additional milestone payments. In January 2012, the company was named "the top biotechnology takeover target in 2012" through an industry survey. Onyx president and chief executive officer (CEO) Tony Coles had said that Onyx liked its prospects as an independent company and was focused on bringing new therapies to patients. However, at the end of August 2013, Amgen announced it was acquiring Onyx in an agreed $10.4 billion deal. Initial funding for the formation of Onyx came from biotechnology firm Chiron ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Proteolix
Proteolix, Inc., was a private biotechnology company with headquarters in South San Francisco, California. Proteolix was founded in 2003 based on technology developed by co-founders Dr. Craig Crews (Yale University) and Dr. Raymond J. Deshaies (California Institute of Technology). Drs. Susan Molineaux and Phil Whitcome (deceased) joined Drs. Crews and Deshaies as co-founders. Proteolix was launched based on an $18.2 million A round comprising investments by Latterell Venture Partners, US Venture Partners, Advanced Technology Ventures, and The Vertical Group. Proteolix focused primarily on the proteasome as a therapeutic target. Its lead product candidate, carfilzomib (PR-171), is a tetrapeptide epoxyketone. At the time of its sale (see below), the company had two earlier-stage programs, an orally-bioavailable proteasome inhibitor for oncology (PR-047), and an agent preferentially targeting the immuno form of the proteasome (PR-957), with potential utility in areas such as rheum ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
New Haven, Connecticut
New Haven is a city in the U.S. state of Connecticut. It is located on New Haven Harbor on the northern shore of Long Island Sound in New Haven County, Connecticut and is part of the New York City metropolitan area. With a population of 134,023 as determined by the 2020 U.S. census, New Haven is the third largest city in Connecticut after Bridgeport and Stamford and the principal municipality of Greater New Haven, which had a total 2020 population of 864,835. New Haven was one of the first planned cities in the U.S. A year after its founding by English Puritans in 1638, eight streets were laid out in a four-by-four grid, creating the "Nine Square Plan". The central common block is the New Haven Green, a square at the center of Downtown New Haven. The Green is now a National Historic Landmark, and the "Nine Square Plan" is recognized by the American Planning Association as a National Planning Landmark. New Haven is the home of Yale University, New Haven's biggest taxpayer ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Multiple Myeloma
Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, anemia, kidney dysfunction, and infections may occur. Complications may include amyloidosis. The cause of multiple myeloma is unknown. Risk factors include obesity, radiation exposure, family history, and certain chemicals. There is an increased risk of multiple myeloma in certain occupations. This is due to the occupational exposure to aromatic hydrocarbon solvents having a role in causation of multiple myeloma. Multiple myeloma may develop from monoclonal gammopathy of undetermined significance that progresses to smoldering myeloma. The abnormal plasma cells produce abnormal antibodies, which can cause kidney problems and overly thick blood. The plasma cells can also form a mass in the bone marrow or soft tissue. When one tumor i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Medicinal Chemistry
Medicinal or pharmaceutical chemistry is a scientific discipline at the intersection of chemistry and pharmacy involved with designing and developing pharmaceutical drugs. Medicinal chemistry involves the identification, synthesis and development of new chemical entities suitable for therapeutic use. It also includes the study of existing drugs, their biological properties, and their quantitative structure-activity relationships (QSAR). Medicinal chemistry is a highly interdisciplinary science combining organic chemistry with biochemistry, computational chemistry, pharmacology, molecular biology, statistics, and physical chemistry. Compounds used as medicines are most often organic compounds, which are often divided into the broad classes of small organic molecules (e.g., atorvastatin, fluticasone, clopidogrel) and "biologics" (infliximab, erythropoietin, insulin glargine), the latter of which are most often medicinal preparations of proteins (natural and recombinant ant ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Proteasome Inhibitor
Proteasome inhibitors are drugs that block the action of proteasomes, cellular complexes that break down proteins. They are being studied in the treatment of cancer; and three are approved for use in treating multiple myeloma. Mechanism Multiple mechanisms are likely to be involved, but proteasome inhibition may prevent degradation of pro-apoptotic factors such as the p53 protein, permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways. For example, bortezomib causes a rapid and dramatic change in the levels of intracellular peptides. Examples * The first non-peptidic proteasome inhibitor discovered was the natural product lactacystin. * Disulfiram has been proposed as another proteasome inhibitor. * Epigallocatechin-3-gallate has also been proposed. * Marizomib (salinosporamide A) has started clinical trials for multiple myeloma. * Oprozomib (ONX-0912), delanzomib (CEP-18770) have also started clinical trials. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Epoxomicin
Epoxomicin is a naturally occurring selective proteasome inhibitor with anti-inflammatory activity. It was originally discovered in 1992. Peptide Institute, Inc. Injected, it can induce -like symptoms in rats. Derivatives of epoxomicin include carfilzomib
Carfilzomib, sold under the brand name Kyprolis, is an anti-cancer medication acting as a selective proteasome inhibitor. Chemically, it is a tetrapeptide epoxyketone and an analog of epoxomicin. It was developed by Onyx Pharmaceuticals.
The U. ... .
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Ubiquitin Ligase
A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 to the protein substrate. In simple and more general terms, the ligase enables movement of ubiquitin from a ubiquitin carrier to another thing (the substrate) by some mechanism. The ubiquitin, once it reaches its destination, ends up being attached by an isopeptide bond to a lysine residue, which is part of the target protein. E3 ligases interact with both the target protein and the E2 enzyme, and so impart substrate specificity to the E2. Commonly, E3s polyubiquitinate their substrate with Lys48-linked chains of ubiquitin, targeting the substrate for destruction by the proteasome. However, many other types of linkages are possible and alter a protein's activity, interactions, or localization. Ubiquitination by E3 ligases reg ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Proteolysis
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, but may also occur by intra-molecular digestion. Proteolysis in organisms serves many purposes; for example, digestive enzymes break down proteins in food to provide amino acids for the organism, while proteolytic processing of a polypeptide chain after its synthesis may be necessary for the production of an active protein. It is also important in the regulation of some physiological and cellular processes including apoptosis, as well as preventing the accumulation of unwanted or misfolded proteins in cells. Consequently, abnormality in the regulation of proteolysis can cause disease. Proteolysis can also be used as an analytical tool for studying proteins in the laboratory, and it may also be used in industry, for example in food proc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cancer Research Institute
The Cancer Research Institute (CRI) is a US non-profit organization funding cancer research and based in New York City. They were founded in 1953 to develop immunologically-based treatments for cancer, and despite their name are a funding body for research rather than a research institute themselves, working with other institutes and organizations. It was founded by Helen Coley Nauts and Oliver R. Grace with a $2,000 grant from Nelson Rockefeller. CRI was created in honor of Nauts' father, William Coley (1862–1936), an American orthopedic surgeon and a pioneer of cancer immunotherapy. Like Dr. Coley, the Institute focuses on immunological treatments for cancer, rather than traditional treatments, such as chemotherapy and surgery. The organization offers research grants to students, postdoctoral fellows, and investigators at medical research institutions throughout the world. It also funds clinical trials testing promising immunotherapies in a variety of cancer types and conv ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
