Discovery of small molecule inhibitors that interact with γ-tubulin

Chem Biol Drug Des. 2012 May;79(5):639-52. doi: 10.1111/j.1747-0285.2012.01340.x. Epub 2012 Feb 15.


Recent studies have shown an overexpression of γ-tubulin in human glioblastomas and glioblastoma cell lines. As the 2-year survival rate for glioblastoma is very poor, potential benefit exists for discovering novel chemotherapeutic agents that can inhibit γ-tubulin, which is known to form a ring complex that acts as a microtubule nucleation center. We present experimental evidence that colchicine and combretastatin A-4 bind to γ-tubulin, which are to our knowledge the first drug-like compounds known to interact with γ-tubulin. Molecular dynamics simulations and docking studies were used to analyze the hypothesized γ-tubulin binding domain of these compounds. The suitability of the potential binding modes was evaluated and suggests the subsequent rational design of novel targeted inhibitors of γ-tubulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Colchicine / chemistry*
  • Colchicine / pharmacokinetics
  • Colchicine / pharmacology*
  • Drug Discovery
  • Humans
  • Molecular Dynamics Simulation
  • Stilbenes / chemistry*
  • Stilbenes / pharmacokinetics
  • Stilbenes / pharmacology*
  • Tubulin / chemistry
  • Tubulin / metabolism*
  • Tubulin Modulators / chemistry*
  • Tubulin Modulators / pharmacokinetics
  • Tubulin Modulators / pharmacology*


  • Stilbenes
  • Tubulin
  • Tubulin Modulators
  • fosbretabulin
  • Colchicine