Immunoconjugates
Tubulin
Polymers
Microtubules
Antineoplastic Agents, Phytogenic
Breast
Chemotherapy, Adjuvant
Lymph Nodes
Carcinoma, Ductal, Breast
Lymphatic Metastasis
Prostate stem cell antigen as therapy target: tissue expression and in vivo efficacy of an immunoconjugate. (1/86)
We conducted an expression analysis of prostate stem cell antigen (PSCA)in normal urogenital tissues, benign prostatic hyperplasia (n = 21), prostatic intraepithelial neoplasia (n = 33), and primary (n = 137) and metastatic (n = 42) prostate adenocarcinoma, using isotopic in situ hybridization on tissue microarrays. In normal prostate, we observe PSCA expression in the terminally differentiated, secretory epithelium; strong expression was also seen in normal urothelium. Forty-eight percent of primary and 64% of metastatic prostatic adenocarcinomas expressed PSCA RNA. Our studies did not confirm a positive correlation between level of PSCA RNA expression and high Gleason grade. We characterized monoclonal anti-PSCA antibodies that recognize PSCA expressed on the surface of live cells, are efficiently internalized after antigen recognition, and kill tumor cells in vitro in an antigen-specific fashion upon conjugation with maytansinoid. Unconjugated anti-PSCA antibodies demonstrated efficacy against PSCA-positive tumors by delaying progressive tumor growth in vivo. Maytansinoid-conjugated antibodies caused complete regression of established tumors in a large proportion of animals. Our results strongly suggest that maytansinoid-conjugated anti-PSCA monoclonal antibodies should be evaluated as a therapeutic modality for patients with advanced prostate cancer. (+info)The biosynthetic gene cluster of the maytansinoid antitumor agent ansamitocin from Actinosynnema pretiosum. (2/86)
Maytansinoids are potent antitumor agents found in plants and microorganisms. To elucidate their biosynthesis at the biochemical and genetic level and to set the stage for their structure modification through genetic engineering, we have cloned two gene clusters required for the biosynthesis of the maytansinoid, ansamitocin, from a cosmid library of Actinosynnema pretiosum ssp. auranticum ATCC 31565. This is a rare case in which the genes involved in the formation of a secondary metabolite are dispersed in separate regions in an Actinomycete. A set of genes, asm22-24, asm43-45, and asm47, was identified for the biosynthesis of the starter unit, 3-amino-5-hydroxybenzoic acid (AHBA). Remarkably, there are two AHBA synthase gene homologues, which may have different functions in AHBA formation. Four type I polyketide synthase genes, asmA-D, followed by the downloading asm9, together encode eight homologous sets of enzyme activities (modules), each catalyzing a specific round of chain initiation, elongation, or termination steps, which assemble the ansamitocin polyketide backbone. Another set of genes, asm13-17, encodes the formation of an unusual "methoxymalonate" polyketide chain extension unit that, notably, seems to be synthesized on a dedicated acyl carrier protein rather than as a CoA thioester. Additional ORFs are involved in postsynthetic modifications of the initial polyketide synthase product, which include methylations, an epoxidation, an aromatic chlorination, and the introduction of acyl and carbamoyl groups. Tentative functions of several asm genes were confirmed by inactivation and heterologous expression. (+info)Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: a phase I, pharmacokinetic, and biologic correlative study. (3/86)
PURPOSE: To determine the maximum tolerated dose and pharmacokinetics of cantuzumab mertansine, an immunoconjugate of the potent maytansine derivative (DM1) and the humanized monoclonal antibody (huC242) directed to CanAg, intravenously (i.v.) once every 3 weeks and to seek evidence of antitumor activity. PATIENTS AND METHODS: Patients with CanAg-expressing solid malignancies were treated with escalating doses of cantuzumab mertansine administered i.v. every 3 weeks. The pharmacokinetic parameters of cantuzumab mertansine, the presence of plasma-shed CanAg, and the development of both human antihuman and human anti-DM1 conjugate antibodies also were characterized. RESULTS: Thirty-seven patients received 110 courses of cantuzumab mertansine at doses ranging from 22 to 295 mg/m2. Acute, transient, and reversible elevations of hepatic transaminases were the principal toxic effects. Nausea, vomiting, fatigue, and diarrhea were common but rarely severe at the highest dose levels. Dose, peak concentration, and area under the concentration-time curve correlated with the severity of transaminase elevation. The mean (+/- SD) clearance and terminal elimination half-life values for cantuzumab mertansine averaged 39.5 (+/-13.1) mL/h/m2 and 41.1 (+/-16.1) hours, respectively. Strong expression (3+) of CanAg was documented in 68% of patients. Two patients with chemotherapy-refractory colorectal carcinoma had minor regressions, and four patients had persistently stable disease for more than six courses. CONCLUSION: The recommended dose for cantuzumab mertansine is 235 mg/m2 i.v. every 3 weeks. The absence of severe hematologic toxic effects, preliminary evidence of cantuzumab mertansine tumor localization, and encouraging biologic activity in chemotherapy-refractory patients warrant further broad clinical development of this immunoconjugate in CanAg-expressing tumors. (+info)Dolastatin 15 binds in the vinca domain of tubulin as demonstrated by Hummel-Dreyer chromatography. (4/86)
The antimitotic depsipeptide dolastatin 15 was radiolabeled with tritium in its amino-terminal dolavaline residue. Dolastatin 15, although potently cytotoxic, is a relatively weak inhibitor of tubulin assembly and does not inhibit the binding of any other ligand to tubulin. The only methodology found to demonstrate an interaction between the depsipeptide and tubulin was Hummel-Dreyer equilibrium chromatography on Sephadex G-50 superfine. The average apparent Kd value obtained in these studies was about 30 microM, with no difference observed when column size or tubulin concentration was varied. This relatively high dissociation constant is consistent with the apparent weak interaction of dolastatin 15 with tubulin demonstrated indirectly in the assembly assay. We attempted to gain insight into the binding site for dolastatin 15 on tubulin by studying inhibitory effects of other drugs when the gel filtration column was equilibrated with both [3H]dolastatin 15 and a second, nonradiolabeled drug. No inhibition was detected with either the colchicine site agent combretastatin A-4 or with an analog of the antimitotic marine peptide diazonamide A (both the analog and diazonamide A are potent inhibitors of tubulin assembly). Weak inhibition was observed with cemadotin, a structural analog of dolastatin 15, and with the depsipeptide cryptophycin 1. Moderate inhibition occurred with vinblastine and vincristine, and strong inhibition with maytansine, halichondrin B, and the peptides dolastatin 10 and phomopsin A. These observations suggest that the binding site(s) for peptide and depsipeptide antimitotic drugs may consist of a series of overlapping domains rather than a well-defined locus on the surface of beta-tubulin. (+info)Cytotoxic activity of trewiasine in 4 human cancer cell lines and 5 murine tumors. (5/86)
Trewiasine (TWS) is a mytansinoid compound. It possessed a significant cytotoxic activity against various human cancer cell lines in vitro. U937 cells, which were more sensitive to the TWS, required TWS 1 microgram.ml-1 to inhibit cell growth over 90% (P less than 0.01). TWS also showed activities against murine tumors in vivo, such as the ascitic tumors S180, hepatoma, U14, and solid tumor Lewis lung carcinoma. Depression of leukocytes was not seen when mice were given ip TWS 10 or 50 micrograms.kg-1.d-1 x 7 d. TWS 0.1-1 micrograms.ml-1 caused no sister chromatid exchange induction in Chinese hamster cell line V79. (+info)Pharmacokinetics and biodistribution of the antitumor immunoconjugate, cantuzumab mertansine (huC242-DM1), and its two components in mice. (6/86)
The humanized monoclonal antibody maytansinoid conjugate, cantuzumab mertansine (huC242-DM1) that contains on average three to four linked drug molecules per antibody molecule was evaluated in CD-1 mice for its pharmacokinetic behavior and tissue distribution, and the results were compared with those of the free antibody huC242. The pharmacokinetics in blood were similar for (125)I-labeled conjugate and antibody with terminal half-lives of 154 and 156 h, respectively. Pharmacokinetic analysis using an enzyme-linked immunosorbent assay (ELISA) method, which measures intact conjugate in plasma samples revealed a faster clearance for the conjugate corresponding to a half-life of 42.2 h. This faster clearance is explained as the result of clearance from circulation and concomitant clearance of drug from circulating conjugate through linker cleavage. An antibody-specific ELISA allowed the determination of the clearance rate of the antibody component from circulation. The drug clearance rate from circulating conjugate was then calculated as the difference between the clearance of the conjugate and the clearance of the antibody component and found to be about three times that of the antibody component. The above results were confirmed with a conjugate, huC242-[(3)H]DM1, where the linked DM1 drugs carried a stable tritium label. Tissue distribution studies with (125)I-labeled conjugate and antibody showed antibody-like behavior for the conjugate; the antibody of the conjugate did not distribute or bind significantly to any solid tissue. (+info)Recent developments in the maytansinoid antitumor agents. (7/86)
Maytansine and its congeners have been isolated from higher plants, mosses and from an Actinomycete, Actinosynnema pretiosum. Many of these compounds are antitumor agents of extraordinary potency, yet phase II clinical trials with maytansine proved disappointing. The chemistry and biology of maytansinoids has been reviewed repeatedly in the late 1970s and early 1980s; the present review covers new developments in this field during the last two decades. These include the use of maytansinoids as "warheads" in tumor-specific antibodies, preliminary metabolism studies, investigations of their biosynthesis at the biochemical and genetic level, and ecological issues related to the occurrence of such typical microbial metabolites in higher plants. (+info)In vitro and in vivo activity of the maytansinoid immunoconjugate huN901-N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine against CD56+ multiple myeloma cells. (8/86)
HuN901 is a humanized monoclonal antibody that binds with high affinity to CD56, the neuronal cell adhesion molecule. HuN901 conjugated with the maytansinoid N(2')-deacetyl-N(2')-(3-mercapto-1-oxopropyl)-maytansine (DM1), a potent antimicrotubular cytotoxic agent, may provide targeted delivery of the drug to CD56 expressing tumors. Based on gene expression profiles of primary multiple myeloma (MM) cells showing expression of CD56 in 10 out of 15 patients (66.6%) and flow cytometric profiles of MM (CD38(bright)CD45(lo)) cells showing CD56 expression in 22 out of 28 patients (79%), we assessed the efficacy of huN901-DM1 for the treatment of MM. We first examined the in vitro cytotoxicity and specificity of huN901-DM1 on a panel of CD56(+) and CD56(-) MM cell lines, as well as a CD56(-) Waldenstrom's macroglobulinemia cell line. HuN901-DM1 treatment selectively decreased survival of CD56(+) MM cell lines and depleted CD56(+) MM cells from mixed cultures with a CD56(-) cell line or adherent bone marrow stromal cells. In vivo antitumor activity of huN901-DM1 was then studied in a tumor xenograft model using a CD56(+) OPM2 human MM cell line in SCID mice. We observed inhibition of serum paraprotein secretion, inhibition of tumor growth, and increase in survival of mice treated with huN901-DM1. Our data therefore demonstrate that huN901-DM1 has significant in vitro and in vivo antimyeloma activity at doses that are well tolerated in a murine model. Taken together, these data provide the framework for clinical trials of this agent to improve patient outcome in MM. (+info)Maytansine is not typically defined in a medical dictionary as it is not a medical term itself, but rather a chemical compound. Maytansine is a natural product that was initially isolated from the bark of the African shrub Maytenus ovatus. It is a potent antimitotic agent, which means it interferes with cell division and has been studied for its potential use in cancer treatment.
In medical contexts, maytansine is often discussed in relation to specific drugs or therapies that utilize this compound. For example, the drug DM1 (also known as maytansinoid 1) is a derivative of maytansine and has been conjugated with monoclonal antibodies for targeted cancer therapy.
Therefore, when discussing 'Maytansine' in a medical context, it generally refers to the chemical compound or its derivatives that have potential use as anticancer agents.
Oxazines are heterocyclic organic compounds that contain a six-membered ring with one nitrogen atom, one oxygen atom, and four carbon atoms. The structure of oxazine is similar to benzene, but with one methine group (=CH−) replaced by a nitrogen atom and another methine group replaced by an oxygen atom.
Oxazines have important applications in the pharmaceutical industry as they are used in the synthesis of various drugs, including anti-inflammatory, antiviral, and anticancer agents. However, oxazines themselves do not have a specific medical definition, as they refer to a class of chemical compounds rather than a medical condition or treatment.
Immunoconjugates are biomolecules created by the conjugation (coupling) of an antibody or antibody fragment with a cytotoxic agent, such as a drug, radionuclide, or toxin. This coupling is designed to direct the cytotoxic agent specifically to target cells, usually cancer cells, against which the antibody is directed, thereby increasing the effectiveness and reducing the side effects of the therapy.
The antibody part of the immunoconjugate recognizes and binds to specific antigens (proteins or other molecules) on the surface of the target cells, while the cytotoxic agent part enters the cell and disrupts its function, leading to cell death. The linker between the two parts is designed to be stable in circulation but can release the cytotoxic agent once inside the target cell.
Immunoconjugates are a promising area of research in targeted cancer therapy, as they offer the potential for more precise and less toxic treatments compared to traditional chemotherapy. However, their development and use also pose challenges, such as ensuring that the immunoconjugate binds specifically to the target cells and not to normal cells, optimizing the dose and schedule of treatment, and minimizing the risk of resistance to the therapy.
Tubulin is a type of protein that forms microtubules, which are hollow cylindrical structures involved in the cell's cytoskeleton. These structures play important roles in various cellular processes, including maintaining cell shape, cell division, and intracellular transport. There are two main types of tubulin proteins: alpha-tubulin and beta-tubulin. They polymerize to form heterodimers, which then assemble into microtubules. The assembly and disassembly of microtubules are dynamic processes that are regulated by various factors, including GTP hydrolysis, motor proteins, and microtubule-associated proteins (MAPs). Tubulin is an essential component of the eukaryotic cell and has been a target for anti-cancer drugs such as taxanes and vinca alkaloids.
Vinblastine is an alkaloid derived from the Madagascar periwinkle plant (Catharanthus roseus) and is primarily used in cancer chemotherapy. It is classified as a vinca alkaloid, along with vincristine, vinorelbine, and others.
Medically, vinblastine is an antimicrotubule agent that binds to tubulin, a protein involved in the formation of microtubules during cell division. By binding to tubulin, vinblastine prevents the assembly of microtubules, which are essential for mitosis (cell division). This leads to the inhibition of cell division and ultimately results in the death of rapidly dividing cells, such as cancer cells.
Vinblastine is used to treat various types of cancers, including Hodgkin's lymphoma, non-Hodgkin's lymphoma, testicular cancer, breast cancer, and others. It is often administered intravenously in a healthcare setting and may be given as part of a combination chemotherapy regimen with other anticancer drugs.
As with any medication, vinblastine can have side effects, including bone marrow suppression (leading to an increased risk of infection, anemia, and bleeding), neurotoxicity (resulting in peripheral neuropathy, constipation, and jaw pain), nausea, vomiting, hair loss, and mouth sores. Regular monitoring by a healthcare professional is necessary during vinblastine treatment to manage side effects and ensure the safe and effective use of this medication.
In the context of medical definitions, polymers are large molecules composed of repeating subunits called monomers. These long chains of monomers can have various structures and properties, depending on the type of monomer units and how they are linked together. In medicine, polymers are used in a wide range of applications, including drug delivery systems, medical devices, and tissue engineering scaffolds. Some examples of polymers used in medicine include polyethylene, polypropylene, polystyrene, polyvinyl chloride (PVC), and biodegradable polymers such as polylactic acid (PLA) and polycaprolactone (PCL).
Microtubules are hollow, cylindrical structures composed of tubulin proteins in the cytoskeleton of eukaryotic cells. They play crucial roles in various cellular processes such as maintaining cell shape, intracellular transport, and cell division (mitosis and meiosis). Microtubules are dynamic, undergoing continuous assembly and disassembly, which allows them to rapidly reorganize in response to cellular needs. They also form part of important cellular structures like centrioles, basal bodies, and cilia/flagella.
Antineoplastic agents, phytogenic, also known as plant-derived anticancer drugs, are medications that are derived from plants and used to treat cancer. These agents have natural origins and work by interfering with the growth and multiplication of cancer cells, helping to slow or stop the spread of the disease. Some examples of antineoplastic agents, phytogenic include paclitaxel (Taxol), vincristine, vinblastine, and etoposide. These drugs are often used in combination with other treatments such as surgery, radiation therapy, and other medications to provide a comprehensive approach to cancer care.
The breast is the upper ventral region of the human body in females, which contains the mammary gland. The main function of the breast is to provide nutrition to infants through the production and secretion of milk, a process known as lactation. The breast is composed of fibrous connective tissue, adipose (fatty) tissue, and the mammary gland, which is made up of 15-20 lobes that are arranged in a radial pattern. Each lobe contains many smaller lobules, where milk is produced during lactation. The milk is then transported through a network of ducts to the nipple, where it can be expressed by the infant.
In addition to its role in lactation, the breast also has important endocrine and psychological functions. It contains receptors for hormones such as estrogen and progesterone, which play a key role in sexual development and reproduction. The breast is also a source of sexual pleasure and can be an important symbol of femininity and motherhood.
It's worth noting that males also have breast tissue, although it is usually less developed than in females. Male breast tissue consists mainly of adipose tissue and does not typically contain functional mammary glands. However, some men may develop enlarged breast tissue due to conditions such as gynecomastia, which can be caused by hormonal imbalances or certain medications.
Breast neoplasms refer to abnormal growths in the breast tissue that can be benign or malignant. Benign breast neoplasms are non-cancerous tumors or growths, while malignant breast neoplasms are cancerous tumors that can invade surrounding tissues and spread to other parts of the body.
Breast neoplasms can arise from different types of cells in the breast, including milk ducts, milk sacs (lobules), or connective tissue. The most common type of breast cancer is ductal carcinoma, which starts in the milk ducts and can spread to other parts of the breast and nearby structures.
Breast neoplasms are usually detected through screening methods such as mammography, ultrasound, or MRI, or through self-examination or clinical examination. Treatment options for breast neoplasms depend on several factors, including the type and stage of the tumor, the patient's age and overall health, and personal preferences. Treatment may include surgery, radiation therapy, chemotherapy, hormone therapy, or targeted therapy.
Adjuvant chemotherapy is a medical treatment that is given in addition to the primary therapy, such as surgery or radiation, to increase the chances of a cure or to reduce the risk of recurrence in patients with cancer. It involves the use of chemicals (chemotherapeutic agents) to destroy any remaining cancer cells that may not have been removed by the primary treatment. This type of chemotherapy is typically given after the main treatment has been completed, and its goal is to kill any residual cancer cells that may be present in the body and reduce the risk of the cancer coming back. The specific drugs used and the duration of treatment will depend on the type and stage of cancer being treated.
Lymph nodes are small, bean-shaped organs that are part of the immune system. They are found throughout the body, especially in the neck, armpits, groin, and abdomen. Lymph nodes filter lymph fluid, which carries waste and unwanted substances such as bacteria, viruses, and cancer cells. They contain white blood cells called lymphocytes that help fight infections and diseases by attacking and destroying the harmful substances found in the lymph fluid. When an infection or disease is present, lymph nodes may swell due to the increased number of immune cells and fluid accumulation as they work to fight off the invaders.
Carcinoma, ductal, breast is a type of breast cancer that begins in the milk ducts (the tubes that carry milk from the lobules of the breast to the nipple). It is called "ductal" because it starts in the cells that line the milk ducts. Ductal carcinoma can be further classified as either non-invasive or invasive, based on whether the cancer cells are confined to the ducts or have spread beyond them into the surrounding breast tissue.
Non-invasive ductal carcinoma (also known as intraductal carcinoma or ductal carcinoma in situ) is a condition where abnormal cells have been found in the lining of the milk ducts, but they have not spread outside of the ducts. These cells have the potential to become invasive and spread to other parts of the breast or body if left untreated.
Invasive ductal carcinoma (IDC) is a type of breast cancer that starts in a milk duct and then grows into the surrounding breast tissue. From there, it can spread to other parts of the body through the bloodstream and lymphatic system. IDC is the most common form of breast cancer, accounting for about 80% of all cases.
Symptoms of ductal carcinoma may include a lump or thickening in the breast, changes in the size or shape of the breast, dimpling or puckering of the skin on the breast, nipple discharge (especially if it is clear or bloody), and/or redness or scaling of the nipple or breast skin. However, many cases of ductal carcinoma are detected through mammography before any symptoms develop.
Treatment for ductal carcinoma depends on several factors, including the stage and grade of the cancer, as well as the patient's overall health and personal preferences. Treatment options may include surgery (such as a lumpectomy or mastectomy), radiation therapy, chemotherapy, hormone therapy, and/or targeted therapies.
Lymphatic metastasis is the spread of cancer cells from a primary tumor to distant lymph nodes through the lymphatic system. It occurs when malignant cells break away from the original tumor, enter the lymphatic vessels, and travel to nearby or remote lymph nodes. Once there, these cancer cells can multiply and form new tumors, leading to further progression of the disease. Lymphatic metastasis is a common way for many types of cancer to spread and can have significant implications for prognosis and treatment strategies.
Estrogen receptors (ERs) are a type of nuclear receptor protein that are expressed in various tissues and cells throughout the body. They play a critical role in the regulation of gene expression and cellular responses to the hormone estrogen. There are two main subtypes of ERs, ERα and ERβ, which have distinct molecular structures, expression patterns, and functions.
ERs function as transcription factors that bind to specific DNA sequences called estrogen response elements (EREs) in the promoter regions of target genes. When estrogen binds to the ER, it causes a conformational change in the receptor that allows it to recruit co-activator proteins and initiate transcription of the target gene. This process can lead to a variety of cellular responses, including changes in cell growth, differentiation, and metabolism.
Estrogen receptors are involved in a wide range of physiological processes, including the development and maintenance of female reproductive tissues, bone homeostasis, cardiovascular function, and cognitive function. They have also been implicated in various pathological conditions, such as breast cancer, endometrial cancer, and osteoporosis. As a result, ERs are an important target for therapeutic interventions in these diseases.
Putterlickia
Maitansine
SLC46A3
Mertansine
List of MeSH codes (D09)
List of MeSH codes (D02)
List of MeSH codes (D04)
Conjugate2
- Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy. (nih.gov)
- T-DM1 is an antibody drug conjugate (ADC) which contains a chemotherapy (maytansine) stably linked to Herceptin. (pharmatimes.com)
Payload2
- T-DM1 retains the antibody functionalities of trastuzumab and adds the potency of a cytotoxic maytansine payload. (biorxiv.org)
- Site-specific conjugation of a maytansine payload. (adcreview.com)
Linker2
- We have developed a trastuzumab-based ADC site-specifically conjugated to maytansine through a noncleavable linker. (biorxiv.org)
- That's a HER2 antibody with a Herceptin-like backbone, but it is linked by a cleavable linker to a type of chemotherapy called maytansine that gets into those cancer cells. (onclive.com)
Cytotoxic agent1
- The eponymous natural cytotoxic agent maytansine is a 19-member lactam (ansa macrolide) structure originally isolated from the Ethiopian shrub Maytenus ovatus. (creativebiolabs.net)
Cancer1
- Maytansine, a cancer drug was later isolated from the same plants in the United States. (or.ke)
Cytotoxic drug2
- SAR3419(huB4-DM4) is a new type of ADC that is composed of a humanized monoclonal IgG1 anti-CD19 antibody (huB4) attached to the potent cytotoxic drug, a maytansine derivative (N2′-deacetyl-N2′-[4-mercapto-4-methyl-1-oxopentyl] [DM4]), through a cleavable disulfide cross-linking agent, N-Succinimidyl-4-2-pyridyldithio butanoic acid (SPDB). (musechem.com)
- This protein has been shown to be an effective transporter of the cytotoxic drug maytansine, which is used in antibody-based targeting of cancer cells. (nih.gov)
Maytansinoid DM41
- Mechanisms by which payload molecules can kill tumor cells include DNA cleavage and cross-linking (calicheamicin, pyrrolobenzodiazepine dimer), microtubule inhibition (auristatin, maleimidocaproyl monomethyl F, maytansine, maytansinoid DM4), topoisomerase inhibition (Deruxtecan, SN-38) and induction of apoptosis (Pseudomonas exotoxin A). Table 1 lists malignancies targeted by ADCs currently in the clinic. (pharmafocusamerica.com)
Calicheamicin1
- The most commonly used cytotoxins for ADCs under clinical development include auristatin, calicheamicin, maytansine and duocarmycin, though auristatin " dominates the market and accounts for over 50% of ADCs in clinical development ," the report says. (biopharma-reporter.com)
Derivative2
- The antibody-drug conjugate trastuzumab-DM1 (T-DM1) was designed to combine the biological activity of trastuzumab with the targeted delivery of a highly potent antimicrotubule agent, DM1 (N-methyl-N-[3-mercapto-1-oxopropyl]-l-alanine ester of maytansinol), a maytansine derivative, to HER2-positive breast cancer cells. (ccij-online.org)
- CPGJ701 is a recombinant humanized anti-human epidermal growth factor receptor-2 (HER2) monoclonal antibody-derivative of the cytotoxic agent maytansine (DM1) conjugate for the treatment of HER2-positive metastatic breast cancer. (zhihuiya.com)
Monoclonal antibody1
- AVE9633 is an antibody-drug conjugate comprising the cytotoxic maytansinoid drug DM4 (N2′-deacetyl-N2′-(4-methyl-4(oxobutyldithio)-1-oxopentyl)-maytansine) linked via disulfide bonds to the anti-CD33 monoclonal antibody huMy9-6. (scienza-under-18.org)
Microtubule2
- Maytansine, a benzoansamacrolide, is a highly potent microtubule-targeted compound that induces mitotic arrest and kills tumor cells at subnanomolar concentrations. (adcreview.com)
- Maytansine and its analogs (maytansinoids DM1 and DM4) are potent microtubule-targeted compounds that inhibit proliferation of cells at mitosis. (adcreview.com)
Potent2
- The potent cell killing ability of maytansine can be used in a targeted delivery approach, such as an antibody-drug conjugate, for the selective delivery of the drug and destruction of cancer cells. (adcreview.com)
- DM4, a structural analogue of maytansine, is usually a new thiol-containing and potent maytansinoid. (scienza-under-18.org)
ADCs1
- ADCs based on the natural product maytansine have been successfully employed clinically. (bvsalud.org)
Cell2
- Maytansine exhibits cytotoxicity against many tumor cell lines and may inhibit tumor growth in vivo. (adcreview.com)
- The authors in this report further explore the maytansine scaffold to develop tubulin inhibitors capable of cell permeation. (bvsalud.org)