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Monomethyl Auristatin F
Monomethyl auristatin F (MMAF) is a synthetic antineoplastic agent. It is part of the approved drug belantamab mafodotin in multiple myeloma and some experimental anti-cancer antibody-drug conjugates such as vorsetuzumab mafodotin and SGN-CD19A. In International Nonproprietary Names for MMAF-antibody-conjugates, the name mafodotin refers to MMAF plus its attachment structure to the antibody. Mechanism of action Monomethyl auristatin F is an antimitotic agent which inhibits cell division by blocking the polymerisation of tubulin. It is linked to an antibody with high affinity to structures on cancer cells, causing MMAF to accumulate in such cells. Chemistry MMAF is actually desmethyl-auristatin F; that is, the N-terminal amino group has only one methyl substituent instead of two as in auristatin F itself. See also * Monomethyl auristatin E Monomethyl auristatin E (MMAE) is a synthetic antineoplastic agent. Because of its toxicity, it cannot be used as a drug itself; instea ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antineoplastic Agent
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a cure, curative intent (which almost always involves combinations of drugs) or it may aim to prolong life or to Palliative care, reduce symptoms (Palliative care, palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called oncology#Specialties, ''medical oncology''. The term ''chemotherapy'' has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce DNA damage (naturally occurring), DNA damage, which is why inhibition of DNA repair can augment chemotherapy. The connotation of the word chemotherapy excludes more selective agents that bl ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Belantamab Mafodotin
Belantamab mafodotin, sold under the brand name Blenrep, is a medication for the treatment of relapsed and refractory multiple myeloma. The most common adverse reactions include keratopathy (corneal epithelium change on eye exam), decreased visual acuity, nausea, blurred vision, pyrexia, infusion-related reactions, and fatigue. Belantamab mafodotin is a humanized IgG1κ monoclonal antibody against the B-cell maturation antigen (BCMA) conjugated with a cytotoxic agent, maleimidocaproyl monomethyl auristatin F (mcMMAF). The antibody-drug conjugate binds to BCMA on myeloma cell surfaces causing cell cycle arrest and inducing antibody-dependent cellular cytotoxicity. Belantamab mafodotin was approved for medical use in the United States and in the European Union in August 2020. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. On November 22, 2022, GSK plc announced it initiated the process for withdrawal of the United States marketing ... [...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] |
Antibody-drug Conjugate
Antibody-drug conjugates or ADCs are a class of biopharmaceutical drugs designed as a targeted therapy for treating cancer. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while sparing healthy cells. As of 2019, some 56 pharmaceutical companies were developing ADCs. ADCs are complex molecules composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug. Antibody-drug conjugates are an example of bioconjugates and immunoconjugates. ADCs combine the targeting properties of Monoclonal antibody, monoclonal antibodies with the cancer-killing capabilities of cytotoxic drugs, designed to discriminate between healthy and diseased tissue. Mechanism of action An anticancer drug is coupled to an antibody that targets a specific tumor antigen (or protein) that, ideally, is only found in or on tumor cells. Antibodies attach themselves to the antigens on the surface of cancerous cells. The biochemical reaction that occurs upon attaching ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Vorsetuzumab Mafodotin
Vorsetuzumab mafodotin (SGN-75) is an antibody-drug conjugate (ADC) directed to the protein CD70 designed for the treatment of cancer. It is a humanized monoclonal antibody, vorsetuzumab, conjugated with noncleavable monomethyl auristatin F (MMAF), a cytotoxic agent. This drug was developed by Seattle Genetics, Inc. The drug completed phase I clinical trials for renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, resp ...,Clinical trials for SGN-7"Clinicaltrials.gov"/ref> but development was discontinued in 2013. No reason was given but SG plan to start clinical trials of SGN-CD70A in 2014. References {{monoclonal-antibody-stub Monoclonal antibodies for tumors Antibody-drug conjugates Experimental cancer drugs ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
SGN-CD19A
Denintuzumab mafodotin (INN; development codes SGN-19A or SGN-CD19A) is a humanized monoclonal antibody-drug conjugate designed for the treatment of CD19-positive acute lymphoblastic leukemia and B-cell non-Hodgkin lymphoma. It consists of an anti-CD19 mAb linked to monomethyl auristatin F (MMAF), a cytotoxic agent. This drug was developed by Seattle Genetics. ''Denintuzumab'' refers to the anti-CD19 antibody, and ''mafodotin'' refers to MMAF and the chemical linkage. Clinical trials The drug is in phase I clinical trials. Preliminary phase I results for B-cell malignancies, including diffuse large B-cell lymphoma Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibody, antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual Incidence (epidemiology), in ... (DLBCL) and B-lineage acute lymphocytic leukemia (B-ALL) were presented at the ASH medical conference Dec 2015. Pha ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antimitotic Agent
A mitotic inhibitor is a drug that inhibits mitosis, or cell division. These drugs disrupt microtubules, which are structures that pull the chromosomes apart when a cell divides. Mitotic inhibitors are used in cancer treatment, because cancer cells are able to grow and eventually spread through the body (metastasize) through continuous mitotic division. Thus, cancer cells are more sensitive to inhibition of mitosis than normal cells. Mitotic inhibitors are also used in cytogenetics (the study of chromosomes), where they stop cell division at a stage where chromosomes can be easily examined. Mitotic inhibitors are derived from natural substances such as plant alkaloids, and prevent cells from undergoing mitosis by disrupting microtubule polymerization, thus preventing cancerous growth. Microtubules are long, ropelike proteins that extend through the cell and move cellular components around. Microtubules are long polymers made of smaller units (monomers) of the protein tubulin. Micro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cell Division
Cell division is the process by which a parent cell (biology), cell divides into two daughter cells. Cell division usually occurs as part of a larger cell cycle in which the cell grows and replicates its chromosome(s) before dividing. In eukaryotes, there are two distinct types of cell division: a vegetative division (mitosis), producing daughter cells genetically identical to the parent cell, and a cell division that produces Haploidisation, haploid gametes for sexual reproduction (meiosis), reducing the number of chromosomes from two of each type in the diploid parent cell to one of each type in the daughter cells. In cell biology, mitosis (Help:IPA/English, /maɪˈtoʊsɪs/) is a part of the cell cycle, in which, replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division gives rise to genetically identical cells in which the total number of chromosomes is maintained. In general, mitosis (division of the nucleus) is preceded by the S stage of interph ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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 cytoskeleton. Microtubules function in many essential cellular processes, including mitosis. Tubulin-binding drugs kill cancerous cells by inhibiting microtubule dynamics, which are required for DNA segregation and therefore cell division. In eukaryotes, there are six members of the tubulin superfamily, although not all are present in all species.Turk E, Wills AA, Kwon T, Sedzinski J, Wallingford JB, Stearns "Zeta-Tubulin Is a Member of a Conserved Tubulin Module and Is a Component of the Centriolar Basal Foot in Multiciliated Cells"Current Biology (2015) 25:2177-2183. Both α and β tubulins have a mass of around 50 kDa and are thus in a similar range compared to actin (with a mass of ~42 kDa). In contrast, tubulin polymers (microtubules) te ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amino
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group (these may respectively be called alkylamines and arylamines; amines in which both types of substituent are attached to one nitrogen atom may be called alkylarylamines). Important amines include amino acids, biogenic amines, trimethylamine, and aniline; Inorganic derivatives of ammonia are also called amines, such as monochloramine (). The substituent is called an amino group. Compounds with a nitrogen atom attached to a carbonyl group, thus having the structure , are called amides and have different chemical properties from amines. Classification of amines Amines can be classified according to the nature and number of substituents on nitrogen. Aliphatic amines contain only H and alkyl substituents. Aroma ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Methyl
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many organic compounds. It is a very stable group in most molecules. While the methyl group is usually part of a larger molecule, bounded to the rest of the molecule by a single covalent bond (), it can be found on its own in any of three forms: methanide anion (), methylium cation () or methyl radical (). The anion has eight valence electrons, the radical seven and the cation six. All three forms are highly reactive and rarely observed. Methyl cation, anion, and radical Methyl cation The methylium cation () exists in the gas phase, but is otherwise not encountered. Some compounds are considered to be sources of the cation, and this simplification is used pervasively in organic chemistry. For example, protonation of methanol gives an elect ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
