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Mertansine
Mertansine, also called DM1 (and in some of its forms emtansine), is a thiol-containing maytansinoid that for therapeutic purposes is attached to a monoclonal antibody through reaction of the thiol group with a linker structure to create an antibody-drug conjugate (ADC). ADCs with this design include trastuzumab emtansine, lorvotuzumab mertansine, and cantuzumab mertansine. Some are still experimental; others are in regular clinical use. Mechanism of action Mertansine is a tubulin inhibitor, meaning that it inhibits the assembly of microtubules by binding to tubulin (at the rhizoxin binding site).National Cancer InstituteDefinition of Maytansine/ref> The monoclonal antibody binds specifically to a structure (usually a protein) occurring in a tumour, thus directing mertansine into this tumour. This concept is called targeted therapy. Uses and chemistry The following (experimental) drugs are antibody-drug conjugates (ADC) combining monoclonal antibodies with mertansine as t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bivatuzumab Mertansine
Bivatuzumab mertansine is a combination of bivatuzumab, a humanized monoclonal antibody, and mertansine, a cytotoxic agent. It is designed for the treatment of squamous cell carcinoma Squamous-cell carcinoma (SCC), also known as epidermoid carcinoma, comprises a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the .... References Monoclonal antibodies for tumors Experimental cancer drugs Antibody-drug conjugates {{antineoplastic-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Lorvotuzumab Mertansine
Lorvotuzumab mertansine (IMGN901) is an antibody-drug conjugate. It comprises the CD56-binding antibody, lorvotuzumab (huN901), with a maytansinoid cell-killing agent, DM1, attached using a disulfide linker, SPP. (When DM1 is attached to an antibody with the SPP linker, it is mertansine; when it is attached with the thioether linker, SMCC, it is emtansine.) Lorvotuzumab mertansine is an experimental agent created for the treatment of CD56 positive cancers (e.g. small-cell lung cancer, ovarian cancer). It has been granted Orphan drug status for Merkel cell carcinoma. It has reported encouraging Phase II results for small-cell lung cancer Small-cell carcinoma, also known as oat cell carcinoma, is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tr .... References Antibody-drug conjugates Experimental cancer drugs Monoclonal antibodie ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cantuzumab Mertansine
Cantuzumab mertansine (SB-408075; huC242-DM1) is an antibody-drug conjugate investigated to treat colorectal cancer and other types of cancer. It is a humanized monoclonal antibody, cantuzumab (huC242) linked to a cytotoxic agent, mertansine (DM1). It was developed by ImmunoGen. Mechanism After the huC242 mab binds to the external domain of CanAg, the cantuzumab mertansine-CanAg complex is internalized, and the DM1 molecules are released intracellularly by cleavage of the DM1-huC242 disulfide bond In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inor ...s. Clinical trials Three phase I clinical studies had reported results by 2003. By 2005, clinical development had been suspended. See also * Cantuzumab ravtansine References Antibody-drug conjugates Monoclonal antibodies f ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Rhizoxin
Rhizoxin is an antimitotic agent with anti-tumor activity. It is isolated from the fungus '' Rhizopus microsporus'' which causes rice seedling blight. Biosynthesis Rhizoxin is biosynthesised by '' Paraburkholderia rhizoxinica'', a bacterial endosymbiont of the fungus ''Rhizopus microsporus''. It is one of a large group of rhizoxin-like compounds produced by the bacteria. The bacterial endosymbiont can be grown independently in culture. This may allow easy harvesting of rhizoxin and the related compounds avoiding total chemical synthesis, although total chemical synthesis is possible. Cytotoxic function Rhizoxin binds beta tubulin in eukaryotic cells disrupting microtubule formation. This, in turn, prevents formation of the mitotic spindle inhibiting cell division. Additionally rhizoxin can depolymerise assembled microtubules.Erratum in J. Antibiot. (Tokyo)., 40 (4), following 565. (1987) The function of rhizoxin is similar to ''Vinca'' alkaloids. Rhizoxin has undergone cli ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Maytansinoid
Maitansine (INN), or maytansine (USAN), is a cytotoxic agent. It inhibits the assembly of microtubules by binding to tubulin at the rhizoxin binding site. The maytansine binding site and binding mode has been characterized. It is a macrolide of the ansamycin type and can be isolated from plants of the genus ''Maytenus''. Maytansinoids Derivatives of maitansine are known as maytansinoids. Some are being investigated as the cytotoxic component of antibody-drug conjugates for cancer treatment, and the antibody-drug conjugate trastuzumab emtansine is an approved drug for the treatment of certain kinds of breast cancer in the EU and in the US. Examples of maytansinoids are: * Ansamitocin *Mertansine / emtansine (DM1) * Ravtansine / soravtansine (DM4) See also * ImmunoGen An immunogen is any substance that generates B-cell (humoral/antibody) and/or T-cell (cellular) adaptive immune responses upon exposure to a host organism. Immunogens that generate antibodies are called antigens ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cantuzumab Mertansine
Cantuzumab mertansine (SB-408075; huC242-DM1) is an antibody-drug conjugate investigated to treat colorectal cancer and other types of cancer. It is a humanized monoclonal antibody, cantuzumab (huC242) linked to a cytotoxic agent, mertansine (DM1). It was developed by ImmunoGen. Mechanism After the huC242 mab binds to the external domain of CanAg, the cantuzumab mertansine-CanAg complex is internalized, and the DM1 molecules are released intracellularly by cleavage of the DM1-huC242 disulfide bond In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inor ...s. Clinical trials Three phase I clinical studies had reported results by 2003. By 2005, clinical development had been suspended. See also * Cantuzumab ravtansine References Antibody-drug conjugates Monoclonal antibodies f ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
HER2/neu
Receptor tyrosine-protein kinase erbB-2 is a protein that normally resides in the membranes of cells and is encoded by the ''ERBB2'' gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently referred to as HER2 (human epidermal growth factor receptor 2) or CD340 ( cluster of differentiation 340). HER2 is a member of the human epidermal growth factor receptor (HER/EGFR/ERBB) family. But contrary to other members of the ERBB family, HER2 does not directly bind ligand. HER2 activation results from heterodimerization with another ERBB member or by homodimerization when HER2 concentration are high, for instance in cancer. Amplification or over-expression of this oncogene has been shown to play an important role in the development and progression of certain aggressive types of breast cancer. In recent years the protein has become an important biomarker and target of therapy for approximately 30% ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Trastuzumab Emtansine
Trastuzumab emtansine, sold under the brand name Kadcyla, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the cytotoxic agent DM1. Trastuzumab alone stops growth of cancer cells by binding to the HER2 receptor, whereas trastuzumab emtansine undergoes receptor-mediated internalization into cells, is catabolized in lysosomes where DM1-containing catabolites are released and subsequently bind tubulin to cause mitotic arrest and cell death. Trastuzumab binding to HER2 prevents homodimerization or heterodimerization (HER2/HER3) of the receptor, ultimately inhibiting the activation of MAPK and PI3K/AKT cellular signalling pathways. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the cytotoxic agent DM1 specifically to tumor cells. The conjugate is abbreviated T-DM1. In the EMILIA clinical trial of women with advanced HER2 positive breas ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
