A clinical drug library screen identifies astemizole as an antimalarial agent

Nat Chem Biol. 2006 Aug;2(8):415-6. doi: 10.1038/nchembio806. Epub 2006 Jul 2.

Abstract

The high cost and protracted time line of new drug discovery are major roadblocks to creating therapies for neglected diseases. To accelerate drug discovery we created a library of 2,687 existing drugs and screened for inhibitors of the human malaria parasite Plasmodium falciparum. The antihistamine astemizole and its principal human metabolite are promising new inhibitors of chloroquine-sensitive and multidrug-resistant parasites, and they show efficacy in two mouse models of malaria.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antimalarials / adverse effects
  • Antimalarials / metabolism
  • Antimalarials / pharmacology*
  • Astemizole / adverse effects
  • Astemizole / analogs & derivatives*
  • Astemizole / metabolism
  • Astemizole / pharmacology*
  • Chloroquine / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Drug Resistance
  • Drug Resistance, Multiple
  • Humans
  • Mice
  • Plasmodium falciparum / drug effects*
  • Plasmodium yoelii / drug effects

Substances

  • Antimalarials
  • Astemizole
  • Chloroquine
  • desmethylastemizole

Associated data

  • PubChem-Substance/11538010
  • PubChem-Substance/11538011
  • PubChem-Substance/11538012
  • PubChem-Substance/11538013
  • PubChem-Substance/11538014
  • PubChem-Substance/11538015