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- W786135223 abstract "The high cost and protracted timeline of new drug discovery is a major roadblock to creating therapies for diseases common in the developing world. One way to sidestep this barrier is to identify new uses for existing drugs. Because the toxicity and clinical properties of existing drugs are known, any novel therapeutic uses identified can be rapidly translated into the clinic without lengthy and expensive pre-clinical and phase I clinical trials. We created and screened a library of 2,450 existing drugs for inhibitors of P. falciparum proliferation using [3H]-hypoxanthine incorporation. The non-sedating antihistamine astemizole and its principal human metabolite desmethylastemizole were identified as potent inhibitors of chloroquine-sensitive and -resistant parasites. Astemizole inhibits heme crystallization, concentrates within the P. falciparum food vacuole, and co-purifies with hemozoin from chloroquine-sensitive and -resistant parasites. Importantly, astemizole is equally effective against multidrug-resistant P. falciparum. In mice infected with chloroquine-resistant P. yoelii astemizole and desmethylastemizole reduced parasitemia with an apparent IC50 of 15 mg/m2, which is near the dose used to treat allergic rhinitis. These results suggest astemizole is promising for the treatment of malaria, and highlight the potential of finding new treatments for diseases of the developing world by screening libraries of existing drugs. This work was supported by The Johns Hopkins Malaria Research Institute and The Johns Hopkins Fund for Medical Discovery." @default.
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- W786135223 date "2006-03-01" @default.
- W786135223 modified "2023-09-27" @default.
- W786135223 title "Identification of astemizole as an anti‐malarial agent by screening a clinical drug library" @default.
- W786135223 doi "https://doi.org/10.1096/fasebj.20.5.a938" @default.
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