Targeting Myosin by Blebbistatin Derivatives: Optimization and Pharmacological Potential.

@article{Rauscher2018TargetingMB,
  title={Targeting Myosin by Blebbistatin Derivatives: Optimization and Pharmacological Potential.},
  author={Anna {\'A}. Rauscher and M{\'a}t{\'e} Gyimesi and Mih{\'a}ly Kov{\'a}cs and Andr{\'a}s M{\'a}ln{\'a}si-Csizmadia},
  journal={Trends in biochemical sciences},
  year={2018},
  volume={43 9},
  pages={
          700-713
        }
}

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TLDR
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The specificity and potency of Blebbistatin are examined by assaying its effects on the actin-activated MgATPase assay of diverse members of the myosin superfamily, and smooth muscle which is highly homologous to vertebrate nonmuscle myOSin is only poorly inhibited.

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TLDR
The property that blebbistatin blocks myosin II in an actin-detached state makes the compound useful both in muscle physiology and in exploring the cellular function of cytoplasmic myOSin II isoforms, whereas the stabilization of a specificMyosin intermediate confers a great potential in structural studies.

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TLDR
It is found that the A456F mutation renders SmM and NM2s resistant to blebbistatin without greatly altering their motor activities or phosphorylation-dependent regulation, making A457F a useful mutant for investigating the cellular function ofNM2s.

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TLDR
It is surmised that blebbistatin inhibits the ATPase activity of NMIIB S1 primarily by blocking entry into the strong binding state; secondarily, it reduces the rate of ADP release.

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TLDR
The discovery of an allosteric site that modulates myosin motor function with high specificity that opens the path toward new therapeutic solutions is reported, illustrating the potential of targeting transition intermediates of molecular machines to develop exquisitely selective pharmacological agents.

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TLDR
Due to its drastically improved solubility and photochemical feature, as well as lack of photo- or cytotoxicity, para-aminoblebbistsatin may become a feasible replacement for blebbistatin, especially at applications when high concentrations of the inhibitor or blue light irradiation is required.
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