YHHU0895, a novel synthetic small-molecule microtubule-destabilizing agent, effectively overcomes P-glycoprotein-mediated tumor multidrug resistance

Cancer Lett. 2012 Jan 1;314(1):54-62. doi: 10.1016/j.canlet.2011.09.013. Epub 2011 Sep 19.


P-glycoprotein-mediated multidrug resistance (MDR) is a major limiting factor in the efficacy of most microtubule-targeting agents. Here, we investigated the novel, synthetic, and small-molecule microtubule-destabilizing agent, 2-(2-amino-5-(1-ethyl-1H-indol-5-yl) pyrimidin-4-yl) phenol (YHHU0895), for its anti-tumor activity and potential for overcoming P-glycoprotein-mediated MDR. YHHU0895 inhibited purified tubulin polymerization through binding to tubulin at the colchicine-binding site and significantly inhibited human tumor cell proliferation. Notably, P-glycoprotein-overexpressing KBV200 and K562/ADR cells, which are strongly resistant to colchicine, vinorelbine and paclitaxel, were sensitive to YHHU0895 both in vitro and in vivo. These findings indicate that YHHU0895 is a novel type of microtubule-destabilizing agent that has the potential for the treatment of patients with drug resistance mediated by P-glycoprotein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / physiology*
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Indoles / pharmacology*
  • Mice
  • Microtubules / drug effects*
  • Polymerization
  • Pyrimidines / pharmacology*
  • Tubulin / metabolism
  • Xenograft Model Antitumor Assays


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents
  • Indoles
  • Pyrimidines
  • Tubulin
  • YHHU0895