As a leading chemical supplier, BOC Sciences provides multiple antibody drug-conjugates (ADCs) cytotoxins and linkers products to support your production. We have demonstrated strong expertise in synthetic chemistry, and all of our products require defined impurity profiles and strictly controlled processes. Furthermore, we also provide customers with a variety of ADCs conjugation services to support customers' research.
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Antibody drug-conjugates (ADCs) technology is a rapidly evolving modality for targeted drug delivery. It consists of a drug compound, usually a cytotoxic molecule, linked to a tumour-targeting antibody such that the toxin is released specifically into the cancer cell at an appropriate time, ideally without affecting other cells. The successful development of ADCs relies on the selection of appropriate target antigens. Improving the safety and efficacy of ADCs is largely dependent on target selection and its interactions. As one of the important targets of ADCs, microtubules are the main components of the cytoskeleton and play an important role in the process of cell division. Due to the rapid proliferation of tumor cells, tubulin inhibitors that interfere with the mitosis of tumor cells have become one of the directions of tumor drug development.
Fig. 1. Microtubule structure and dynamics (Developmental Cell, 54(1): 7-20).
The microtubular cytoskeleton controls many vital functions in eukaryotic cells ranging from cell division to cell movement and vesicular transport. Microtubules are cytoskeletal filaments with an outer diameter of approximately 25nm, and are composed of heterodimers of globular α-tubulin and β-tubulin molecules. As they are hollow cylinders, microtubules are mechanically rigid, thus allowing their assembly into large intracellular structures. These structures are essential for cell function and include mitotic and meiotic spindles, which ensure the correct division of cells, axonemes, which are the central molecular machines of cilia and flagella, and the neuronal cytoskeleton, which controls the connectivity and function of neurons. Therefore, microtubules and tubulin are the targets for a number of highly effective drugs currently available for the treatment of cancer, and for many new drugs in various stages of development.
Due to the importance of microtubules in cells, particularly in rapidly dividing cells, compounds that bind microtubules, called microtubule targeting agents (MTAs), have long been one of the most important drug classes for cancer chemotherapy. MTAs suppress and alter tubulin dynamics, therefore disrupting dependent cellular processes. Treatment with all MTAs results in cell cycle arrest during the late G2/M phase at the metaphase/anaphase transition due to inhibiting the separation of sister chromatids to the poles, leading to apoptosis. Microtubule inhibitors mainly inhibit or promote the tubulin polymerization. Among them, the agent that promotes tubulin polymerization acts on the β-subunit of α-β tubulin dimer, so that the microtubules growth is not regulated, such as MMAE and MMAF. Inhibitors of tubulin polymerization block the polymerization of tubulin dimers by inhibiting the formation of mature microtubules, such as DM1 and DM4.