ONX-0801
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ONX-0801
ONX-0801 (BGC 945) is an experimental drug that has been developed to target ovarian cancer. It is a folate receptor alpha mediated thymidylate synthase inhibitor. ONX-0801 was originally developed by BTG and the Institute of Cancer Research in the UK, and subsequently licensed to Onyx Pharmaceuticals for clinical development. It is designed to selectively target tumour tissues of certain kinds of cancer. It is poorly absorbed into most cells, but is actively transported by folate receptor alpha (FRα), which is usually only expressed at low levels in the apical membrane of some specialised tissues, but is expressed at much higher levels in some subtypes of ovarian cancer. This causes the drug to accumulate selectively in tumour tissues, while healthy tissues are only exposed to a much lower concentration. In 2017, it received press coverage following the successful completion of a Phase I clinical trial The phases of clinical research are the stages in which scientists co ...
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Folate Receptor Alpha
Folate receptor 1 (Folate receptor alpha, FOLR1) is a protein that in humans is encoded by the ''FOLR1'' gene. The protein encoded by this gene is a member of the folate receptor (FOLR) family. Members of this family have a high affinity for folic acid and for several reduced folic acid derivatives, and mediate delivery of 5-methyltetrahydrofolate to the interior of cells. Functions This receptor is responsible for binding to folic acid and its derivatives, which becomes crucial during fetal development. By adding folate supplementation during pregnancy, neural tube defects in the fetus are prevented. Folate derivatives are necessary for important metabolic processes such as DNA, protein and lipid methylation. More importantly, folate plays a major role in DNA replication and cell division, which are common characteristics of rapid growth. Even though it is unclear how folate affects neural tube formation, scientists are certain that without appropriate folate levels, neural tub ...
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Ovarian Cancer
Ovarian cancer is a cancerous tumor of an ovary. It may originate from the ovary itself or more commonly from communicating nearby structures such as fallopian tubes or the inner lining of the abdomen. The ovary is made up of three different cell types including epithelial cells, germ cells, and stromal cells. When these cells become abnormal, they have the ability to divide and form tumors. These cells can also invade or spread to other parts of the body. When this process begins, there may be no or only vague symptoms. Symptoms become more noticeable as the cancer progresses. These symptoms may include bloating, vaginal bleeding, pelvic pain, abdominal swelling, constipation, and loss of appetite, among others. Common areas to which the cancer may spread include the lining of the abdomen, lymph nodes, lungs, and liver. The risk of ovarian cancer increases with age. Most cases of ovarian cancer develop after menopause. It is also more common in women who have ovulated m ...
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Thymidylate Synthase Inhibitor
Thymidylate synthase inhibitors are chemical agents which inhibit the enzyme thymidylate synthase and have potential as an anticancer chemotherapy. This inhibition prevents the methylation of C5 of deoxyuridine monophosphate (dUMP) thereby inhibiting the synthesis of deoxythymidine monophosphate (dTMP). The downstream effect is promotion of cell death because cells would not be able to properly undergo DNA synthesis if they are lacking dTMP, a necessary precursor to dTTP. Five agents were in clinical trials in 2002: raltitrexed, pemetrexed, nolatrexed, ZD9331, and GS7904L. Examples include * Raltitrexed, used for colorectal cancer since 1998 * Fluorouracil, used for colorectal cancer * BGC 945 * OSI-7904L OSI-7904 is a noncompetitive liposomal thymidylate synthase inhibitor. OSI-7904 is a benzoquinazoline folate analog with antineoplastic activity. As a thymidylate synthase inhibitor, OSI-7904 noncompetitively binds to thymidylate synthase, resu ... References Ant ...
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BTG Plc
BTG Limited is an international specialist healthcare company that is developing and commercialising products targeting critical care, cancer and other disorders. The current name was adopted when the British Technology Group changed its name on 27 May 1998. BTG was a constituent of the FTSE 250 Index until it was acquired by Boston Scientific in August 2019. History In 1948, the National Research Development Corporation was formed with the purpose of commercialising innovations that arose from public funded research. This was complemented in November 1975 by the establishment of the National Enterprise Board to implement the then-Government's policy of moving public sector industry into commercial private enterprise. These two organisations were merged by the Government in 1981 to form a new, non-statutory body called the British Technology Group. It acted principally to license and commercialise the use of publicly funded developments. The Group was put onto a statutory footing ...
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Institute Of Cancer Research
The Institute of Cancer Research (the ICR) is a public research institute and a member institution of the University of London in London, United Kingdom, specialising in oncology. It was founded in 1909 as a research department of the Royal Marsden Hospital and joined the University of London in 2003. It has been responsible for a number of breakthrough discoveries, including that the basic cause of cancer is damage to DNA. The ICR occupies sites in Chelsea, Central London and Sutton, southwest London. The ICR provides both taught postgraduate degree programmes and research degrees and currently has around 340 students. Together with the Royal Marsden Hospital the ICR forms the largest comprehensive cancer centre in Europe, and was ranked first amongst all British higher education institutions in the ''Times Higher Education'' 2014 Research Excellence Framework Table of Excellence. In clinical medicine, 83% and in biological sciences, 96% of the ICR's academic research was asse ...
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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 ...
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Apical Membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the extracellular space). The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols (a lipid component) interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of cells and organelles, being selectively permeable to ions an ...
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Phase I Clinical Trial
The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases start with testing for safety in a few human subjects, then expand to many study participants (potentially tens of thousands) to determine if the treatment is effective. Clinical research is conducted on drug candidates, vaccine candidates, new medical devices, and new diagnostic assays. Summary Clinical trials testing potential medical products are commonly classified into four phases. The drug development process will normally proceed through all four phases over many years. If the drug successfully passes through Phases I, II, and III, it will usually be approved by the national regulatory authority for use in the general population. Phase IV trials are 'post-marketing' or 'surveillance' studies conducted to monitor safety over severa ...
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