Non-muscle myosin II is a promising therapeutic target

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  Figure 1.. Pharmacological inhibition of non-muscle myosin II (NMII) family members has therapeutic potential in a wide array of diseases, and oxidative stress is one mechanism whereby such inhibition produces a benefit in cancer. (A) Upper panel: NMII consists of two heavy chains. These are composed of three domains: (i) two motor domains at the amino terminus (right side of image) that contain the ATPase site and which bind to blebbistatin and its derivatives, (ii) the lever arm, containing the essential and regulatory light chains (middle, blue and magenta), and (iii) the C-terminal coiled coil (left side of image), which allows NMII to polymerize into minifilaments. Lower panel: illustration of the diverse diseases (upper portion of each box) that depend on an array of NMII functions (lower portion of each box). (B) Inhibiting NMIIA and NMIIB with MT-125 prevents mitochondrial fission. This is a quality control process that removes damaged segments of the mitochondrial membrane that would otherwise leak reactive oxygen species (ROS) into the cytoplasm, where it can damage DNA in the nucleus and peroxidize the cell membrane. This has two potentially therapeutic effects. First, it enables…