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Vascular Disrupting Agent
A vascular-targeting agent (VTA) or vascular disrupting agent (VDA) is a drug designed to damage the vasculature (blood vessels) of cancer tumors causing central necrosis. VTAs can be small-molecule or ligand-based. Small-molecule VTAs include: * microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 an ... destabilizing drugs such as combretastatin A-4 disodium phosphate (CA4P), ZD6126, AVE8062, Oxi 4503 * vadimezan (ASA404) Clinical trials Phase II : ZD6126, CA4P, plinabulin (NPI-2358) Phase III : DMXAA (ASA404). References {{antineoplastic-drug-stub Cancer treatments Drugs acting on the cardiovascular system ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Blood Vessel
The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also take waste and carbon dioxide away from the tissues. Blood vessels are needed to sustain life, because all of the body's tissues rely on their functionality. There are five types of blood vessels: the arteries, which carry the blood away from the heart; the arterioles; the capillaries, where the exchange of water and chemicals between the blood and the tissues occurs; the venules; and the veins, which carry blood from the capillaries back towards the heart. The word ''vascular'', meaning relating to the blood vessels, is derived from the Latin ''vas'', meaning vessel. Some structures – such as cartilage, the epithelium, and the lens and cornea of the eye – do not contain blood vessels and are labeled ''avascular''. Etymology * artery: late Middle English; from Latin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans. Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as ''Helicobacter pylori'', hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV). These factors act, at least partly, by changing the genes of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, when it may be called a tumor. ICD-10 classifies neoplasms into four main groups: benign neoplasms, in situ neoplasms, malignant neoplasms, and neoplasms of uncertain or unknown behavior. Malignant neoplasms are also simply known as cancers and are the focus of oncology. Prior to the abnormal growth of tissue, as neoplasia, cells often undergo an abnormal pattern of growth, such as metaplasia or dysplasia. However, metaplasia or dysplasia does not always progress to neoplasia and can occur in other conditions as well. The word is from Ancient Greek 'new' and 'formation, creation'. Types A neoplasm can be benign, potentially m ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Necrosis
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated digestion of cell components. In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death. While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal. Cellular death due to necrosis does not follow the apoptotic signal transduction pathway, but rather various receptors are activated and result in the loss of cell membrane integrity and an uncontrolled release of products of cell death into the extracellular space. This initiates in the surrounding tissue an inflammatory response, which attracts leukocytes and nearby phagocytes which eliminate the dead cells by phagocytosis. However, microbial damaging substances released by leukocytes would crea ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ligand (biochemistry)
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix. The relationship between ligand and binding partner is a function of charge, hydrophobicity, and molecular structure. Binding occurs by intermolecular forces, such as ionic bonds, hydrogen bonds and Van der Waals forces. The association or docking is actually reversible through dissociation. Measurably irreversible covalent bonding between a ligand and target molecule is atypical in biological systems. In contrast to the definition of lig ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Microtubule
Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nm and have an inner diameter between 11 and 15 nm. They are formed by the polymerization of a dimer of two globular proteins, alpha and beta tubulin into protofilaments that can then associate laterally to form a hollow tube, the microtubule. The most common form of a microtubule consists of 13 protofilaments in the tubular arrangement. Microtubules play an important role in a number of cellular processes. They are involved in maintaining the structure of the cell and, together with microfilaments and intermediate filaments, they form the cytoskeleton. They also make up the internal structure of cilia and flagella. They provide platforms for intracellular transport and are involved in a variety of cellular processes, including the movement of secretory vesicles, organell ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Combretastatin A-4 Disodium Phosphate
Fosbretabulin (also known as combretastatin A-4 phosphate or CA4P) is a microtubule destabilizing experimental drug, a type of vascular-targeting agent, a drug designed to damage the vasculature (blood vessels) of cancer tumours causing central necrosis. It is a derivative of combretastatin. It is formulated as the salts fosbretabulin disodium and fosbretabulin tromethamine. Fosbretabulin is a prodrug. ''In vivo'', it is dephosphorylated to its active metabolite, combretastatin A-4. In July 2007, the pharmaceutical company OXiGENE initiated a 180-patient phase III clinical trial of fosbretabulin in combination with carboplatin for the treatment of anaplastic thyroid cancer. There is currently no fully FDA approved treatment for this form of cancer. By 2017, it had completed multiple clinical trials (e.g. for solid tumours, non-small cell lung cancer) with more in progress. See also * Combretastatin Combretastatin is a dihydrostilbenoid found in '' Combretum caffrum''. As ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
ZD6126
ZD6126 is a vascular-targeting agent and a prodrug of N-acetylcolchinol, related to colchicine. It has shown promising results on tumors in mice. A phase I clinical trial identified gastrointestinal and cardiac effects as limiting dosing. Two phase II clinical trials were suspended investigating ZD6126 in metastatic renal cell carcinoma and metastatic colorectal cancer. ZD6126 was being investigated by AstraZeneca as a vascular disrupting agent A vascular-targeting agent (VTA) or vascular disrupting agent (VDA) is a drug designed to damage the vasculature (blood vessels) of cancer tumors causing central necrosis. VTAs can be small-molecule or ligand-based. Small-molecule VTAs include: * ... (VDA). However, the trials were halted, after it became apparent that ZD6126 was too cardiotoxic at the required doses. References Phenol ethers Acetamides Abandoned drugs {{antineoplastic-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
AVE8062
Ombrabulin was an experimental drug candidate discovered by Ajinomoto and further developed by Sanofi-Aventis. Ombrabulin is a combretastatin A-4 derivative that exerts its antitumor effect by disrupting the formation of blood vessels needed for tumor growth. It was granted orphan drug status by the European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ... in April 2011. In January 2013, Sanofi said it discontinued development of ombrabulin after disappointing results from phase III clinical trials. References {{reflist Experimental cancer drugs Amino acid derivatives ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vadimezan
Vadimezan (also known as or ASA404 and dimethylxanthone acetic acid or DMXAA) is a tumor-vascular disrupting agent (tumor-VDA) that attacks the blood supply of a cancerous tumor to cause tumor regression. Clinical trials Non-small cell lung cancer Despite positive results at the preclinical stage, vadimezan failed in human clinical trials. Studies have demonstrated the reason for the inefficacy. Vadimezan was shown to target the STING pathway, however, this effect is mouse specific; it has no effect on human STING. A single amino acid difference at position 162 (S162A) of the cyclic-dinucleotide-binding site of STING makes mouse STING sensitive to the drug, whereas human STING remains insensitive. Vadimezan had been studied in combination with chemotherapy in at least two Phase II trials for advanced non-small cell lung cancer (NSCLC) and showed survival extensions of around 5 months when compared to chemotherapy alone (14.0 months compared to 8.8 months). [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Plinabulin
Plinabulin (provisional name BPI-2358, formerly NPI-2358) is a small molecule under development by BeyondSpring Pharmaceuticals, and is in a world-wide Phase 3 clinical trial for non-small cell lung cancer. Plinabulin is being investigated for the reduction of chemotherapy-induced neutropenia and for anti-cancer effects in combination with immune checkpoint inhibitors and in KRAS mutated tumors. Plinabulin blocks the polymerization of tubulin Tubulin in molecular biology can refer either to the tubulin protein superfamily of globular proteins, or one of the member proteins of that superfamily. α- and β-tubulins polymerize into microtubules, a major component of the eukaryotic cytoske ... in a unique manner, resulting in multi-factorial effects including an enhanced immune-oncology response, activation of the JNK pathway and disruption of the tumor blood supply. References {{reflist Diketopiperazines Imidazoles Experimental cancer drugs Tert-butyl compounds ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
