The antitumor agent 3-bromopyruvate has a short half-life at physiological conditions

Biochem Biophys Res Commun. 2014 Sep 12;452(1):170-3. doi: 10.1016/j.bbrc.2014.08.066. Epub 2014 Aug 21.

Abstract

Clinical research is currently exploring the validity of the anti-tumor candidate 3-bromopyruvate (3-BP) as a novel treatment for several types of cancer. However, recent publications have overlooked rarely-cited earlier work about the instability of 3-BP and its decay to 3-hydroxypyruvate (3-HP) which have obvious implications for its mechanism of action against tumors, how it is administered, and for precautions when preparing solutions of 3-BP. This study found the first-order decay rate of 3-BP at physiological temperature and pH has a half-life of only 77 min. Lower buffer pH decreases the decay rate, while choice of buffer and concentration do not affect it. A method for preparing more stable solutions is also reported.

Keywords: 3-Bromopyruvate; 3-Hydroxypyruvate; Alkylating agent; Cancer therapy; Ketone hydration; Tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Half-Life
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy
  • Pyruvates / pharmacokinetics
  • Pyruvates / therapeutic use*

Substances

  • Antineoplastic Agents
  • Pyruvates
  • bromopyruvate