Targeting Myosin by Blebbistatin Derivatives: Optimization and Pharmacological Potential

Trends Biochem Sci. 2018 Sep;43(9):700-713. doi: 10.1016/j.tibs.2018.06.006. Epub 2018 Jul 26.

Abstract

Blebbistatin is a widely used inhibitor of myosin 2 that enables the study of a broad range of cytoskeleton-related processes. However, blebbistatin has several limitations hindering its applicability: it is fluorescent, poorly water soluble, cytotoxic, and prone to (photo)degradation. Despite these adverse effects, being the only available myosin 2-specific inhibitor, blebbistatin is rather a choice of necessity. Blebbistatin has been modified to improve its properties and some of the new compounds have proven to be useful replacements of the original molecule. This review summarizes recent results on blebbistatin development. We also discuss the pharmacological perspectives of these efforts, as myosins are becoming promising drug target candidates for a variety of conditions ranging from neurodegeneration to muscle disease, wound healing, and cancer metastasis.

Keywords: cytotoxicity; drug development; fluorescence; inhibition; selectivity; solubility.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Delivery Systems / methods*
  • Heterocyclic Compounds, 4 or More Rings* / pharmacokinetics
  • Heterocyclic Compounds, 4 or More Rings* / therapeutic use
  • Humans
  • Muscular Diseases* / drug therapy
  • Muscular Diseases* / metabolism
  • Muscular Diseases* / pathology
  • Myosins / antagonists & inhibitors*
  • Myosins / metabolism
  • Neoplasm Metastasis
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism
  • Neoplasms* / pathology
  • Neurodegenerative Diseases* / drug therapy
  • Neurodegenerative Diseases* / metabolism
  • Neurodegenerative Diseases* / pathology
  • Wound Healing / drug effects*

Substances

  • Heterocyclic Compounds, 4 or More Rings
  • blebbistatin
  • Myosins