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Tubulin Maytansine Site Binding Ligands and Their Applications as MTAs and ADCs for Cancer Therapy.

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Microtubule targeting agents (MTAs) represent the most successful anticancer drugs for cancer chemotherapy. Through interfering with the tubulin polymerization and depolymerization dynamics, MTAs influence intracellular transport and cell signal pathways, inhibit cell mitosis and cell

Metabolism studies of the anti-tumor agent maytansine and its analog ansamitocin P-3 using liquid chromatography/tandem mass spectrometry.

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Maytansine, a potent clinically evaluated plant-derived anti-tumor drug, and its microbial counterpart, ansamitocin P-3, showed a substantially higher cytoxicity than many other anti-tumor drugs. Owing to a shortage of material and lack of sufficiently sensitive analytical methods at the time, no

Minimal single-agent activity of maytansine in refractory breast cancer: a Southwest Oncology Group study.

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Maytansine is an experimental antitumor agent that has shown minimal efficacy against breast cancer with minimal myelosuppression in phase I trials. Forty-one patients with advanced drug-resistant breast cancer were treated with a 5-day intermittent iv infusion of maytansine repeated every 21 days.

Phase II trials of maytansine, low-dose chlorozotocin, and high-dose chlorozotocin as single agents against advanced measurable adenocarcinoma of the pancreas. Gastrointestinal Tumor Study Group.

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One hundred and five patients with advanced measurable pancreatic carcinoma were randomized to receive therapy with maytansine, low-dose chlorozotocin (120 mg/m2), or high-dose chlorozotocin (175 mg/m2). Objective response rates were as follows: maytansine, no responses among 48 patients; low-dose

Semisynthetic maytansine analogues for the targeted treatment of cancer.

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Maytansine, a highly cytotoxic natural product, failed as an anticancer agent in human clinical trials because of unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach for the selective destruction of cancer cells. A series of new

Zein nanoparticles as nontoxic delivery system for maytansine in the treatment of non-small cell lung cancer.

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Purpose: Maytansine (DM1) is a potent anticancer drug and limited in clinical application due to its poor water solubility and toxic side effects. Zein is widely used in nano drug delivery systems due to its good biocompatibility. In this study, we prepared DM1-loaded zein nanoparticles

Aptamer Enables Consistent Maytansine Delivery Through Maintaining Receptor Homeostasis for HER2 Targeted Cancer Therapy

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Although the extensive clinical use of the ADC trastuzumab-DM1(T-DM1) for human epidermal growth factor receptor 2 (HER2) targeted cancer therapy, many patients who initially respond to T-DM1 treatment eventually met the insufficient efficacy issue, which is partly attributed to the decreased amount

Antibody-DM1 conjugates as cancer therapeutics.

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Synthetic derivatives of the microtubule-targeted agent maytansine, commonly known as drug maytansinoids or DMs, are emerging as potential cancer therapeutics. DM1 is an antibody-conjugatable maytansinoid that was developed to overcome systemic toxicity associated with maytansine and to enhance

Trastuzumab Emtansine: A Review of Its Adjuvant Use in Residual Invasive HER2-Positive Early Breast Cancer

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Trastuzumab emtansine (Kadcyla^®), an antibody-drug conjugate of trastuzumab (Herceptin^®) connected by a thioether linker to the microtubule inhibitor DM1 (a cytotoxic derivative of maytansine), provides direct intracellular delivery of the potent cytotoxin DM1 to

Trastuzumab emtansine in advanced human epidermal growth factor receptor 2-positive breast cancer.

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BACKGROUND Ado- trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate composed of trastuzumab, a stable linker (MCC), and the cytotoxic agent DM1 (derivative of maytansine; mertansine). T-DM1 retains the mechanisms of action of

Novel approaches to target HER2-positive breast cancer: trastuzumab emtansine.

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The human epidermal growth factor receptor 2 (HER2) is overexpressed in 20% of breast carcinomas. Prior to the development of targeted therapies, HER2-positive breast cancer was associated with more aggressive disease and poor prognosis. Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate

A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin.

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Microtubule-targeting agents (MTAs) like taxol and vinblastine are among the most successful chemotherapeutic drugs against cancer. Here, we describe a fluorescence anisotropy-based assay that specifically probes for ligands targeting the recently discovered maytansine site of tubulin. Using this

Trastuzumab emtansine in breast cancer.

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BACKGROUND Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (HER2)-targeted antibody-drug conjugate (ADC) composed of trastuzumab, a stable linker (MCC), and the cytotoxic agent DM1 (derivative of maytansine). Administration of T-DM1 leads to limited systemic exposure of

Aptamer-Drug Conjugates of Active Metabolites of Nucleoside Analogs and Cytotoxic Agents Inhibit Pancreatic Tumor Cell Growth.

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Aptamer-drug conjugates (ApDCs) have the potential to improve the therapeutic index of traditional chemotherapeutic agents due to their ability to deliver cytotoxic drugs specifically to cancer cells while sparing normal cells. This study reports on the conjugation of cytotoxic drugs to an aptamer

Trastuzumab emtansine: a unique antibody-drug conjugate in development for human epidermal growth factor receptor 2-positive cancer.

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Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor (HER2)-targeted antibody-drug conjugate, composed of trastuzumab, a stable thioether linker, and the potent cytotoxic agent DM1 (derivative of maytansine), in phase III development for HER2-positive cancer. Extensive analysis

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