Myoseverin

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Background

IC50: 16 nMMyoseverin is a novel microtubule-binding molecule.Microtubules are dynamic filamentous cytoskeletal proteins, which are composed of tubulin and are an critical therapeutic target in tumour cells. Drugs binding to microtubules have been the first-line standard of anticancer therapy for decades and until the advent of targeted therapy.In vitro: Myoseverin was found to be able to induce the reversible fission of multinucleated myotubes into mononucleated fragments. In addition, cell proliferation and myotube fission promoted DNA synthesis after myoseverin removal and transfer of the cells to the fresh growth medium. Moreover, the biochemical analysis and transcriptional profiling showed that myoseverin alone did not reverse the processes of biochemical differentiation. However, myoseverin could affect the expression of various growth factor, extracellular matrix-remodeling, immunomodulatory, as well as stress response genes, which was consistent with the activation of pathways involved in tissue regeneration and wound healing [1]. Another study found that myoseverin-treated cardiac myocytes showed disruptions of the striated Z-bands with alpha-actinin and desmin. Similarly, active stathmin expression did not prevent the assembly of sarcomere. Moreover, the extent of MT destabilization caused by myoseverin and nocodazole were comparable [2].In vivo: Currently, there is no animal in vivo data reported. Clinical trial: Up to now, myoseverin is still in the preclinical development stage.

[1] Rosania GR,Chang YT,Perez O,Sutherlin D,Dong H,Lockhart DJ,Schultz PG. Myoseverin, a microtubule-binding molecule with novel cellular effects. Nat Biotechnol.2000 Mar;18(3):304-8.
[2] Ng DC,Gebski BL,Grounds MD,Bogoyevitch MA. Myoseverin disrupts sarcomeric organization in myocytes: an effect independent of microtubule assembly inhibition. Cell Motil Cytoskeleton.2008 Jan;65(1):40-58.