BOC Sciences provides various toxins used as payloads for antibodies conjugation and form ADCs. Mitochondria are the powerhouse of the cells, which control bioenergetics, biosynthesis, metabolism, and signaling. Given the wide range of roles, mitochondria were studied extensively as a potential therapeutic target for various diseases, including cancer, diabetes, and neurodegenerative diseases. Mitochondrial dysfunction of cancer cells includes increased aerobic glycolysis, elevated ROS level, decreased apoptosis, and resistance to chemotherapeutic agents. On the other hand, normal mitochondria suppress cancer proliferation and increase drug sensitivity by inhibiting cancerous glycolysis and glucose uptake. Mitochondrion-mediated pathways have been identified as promising targets for various diseases.
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Mitochondria are organelles present in most cells and composed of two membrane layers. They are the energy-producing structure in cells and the central spot for aerobic respiration. Mitochondrion retains its own genetic material and system, but is limited in size as a semi-autonomous organelle. In addition to supplying energy to cells, mitochondria are also involved in cellular differentiation, information transmission, apoptosis, and the regulation of cell growth and cell cycle. Numerous mitochondrial features have been used to design novel mitochondrial targeting anticancer agents. Moreover, selective delivery of drugs to mitochondria improves drugs' specificity and reduces toxicity. A better understanding of the mitochondrial role in cancer development reveals possible therapeutic targets and improves mitochondria-targeted anticancer drugs' activity and selectivity.
Fig. 1. Structure of Mitochondria.
Mitochondria in malignant cells differ from normal cells in structure and function, which are actively involved in metabolic reprogramming. Mitochondria in cancer cells are characterized by excessive reactive oxygen species (ROS) production, promoting cancer development by inducing genomic instability, altering gene expression, and participating in signaling pathways. Mensacarcin is a highly oxygenated polyketide first isolated from soil-dwelling Streptomyces bacteria. It exhibits potent cytostatic properties (mean of 50% growth inhibition=0.2 μm) in almost all cell lines of the National Cancer Institute (NCI)-60 cell line screen and relatively selective cytotoxicity against melanoma cells. Live-cell bioenergetic flux analysis confirmed that Mensacarcin disturbs mitochondrial function and energy production. Mensacarcin's unique mode of action suggests that it may be a valuable probe for examining energy metabolism, particularly in BRAF-mutant melanoma, and represent a promising lead for developing new anticancer drugs.