A clinical drug library screen identifies astemizole as an antimalarial agent.
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.
Chong
Curtis R
CR
Department of Pharmacology and Molecular Sciences. The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Chen
Xiaochun
X
Shi
Lirong
L
Liu
Jun O
JO
Sullivan
David J
DJ
D000818:Animals; D000962:Antimalarials / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D016589:Astemizole / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D018432:Drug Resistance, Multiple; D006801:Humans; D051379:Mice; D010963:Plasmodium falciparum / Q000187:drug effects*; D010967:Plasmodium yoelii / Q000187:drug effects
D000962:Antimalarials; D016589:Astemizole; D002738:Chloroquine; C040463:desmethylastemizole