Repositioning: the fast track to new anti-malarial medicines?

Malaria Journal

Table 1 Summary of compounds tested, in vitro screening methods, and results

Number of compounds	Source	In vitro testing by:	In vitro testing method	No. hits (%)	No. tested *in vivo**
~3,800	• 800 FDA-approved drugs (2008)	SJCRH	• SYBR® I dye DNA staining assay	24 (0.6)	1
	• 2,700 bio-actives (Prestwick, Sigma-Lopac, and MSD)		• P. falciparum 3D7 and K1
	• 296 FDA-approved drugs (2009)
	• 47 ‘anti-proliferative’ compounds
63	GSK discontinued clinical candidates	GSK	• Whole-cell [³H] hypoxanthine radioisotope incorporation	4 (6.4)	0
63	GSK discontinued clinical candidates	GSK	• P. falciparum 3D7A
176	Pfizer STLAR library of discontinued clinical candidates	Discovery biology	• HTS screen using DAPI DNA imaging assay with P. falciparum 3D7 and Dd2	5 (2.8)	1
176		Pfizer	• EC₅₀ determined using SYBR® I dye DNA staining assay with P. falciparum 3D7 and K1
100	AstraZeneca discontinued clinical candidates	AstraZeneca	• SYBR® I dye DNA staining assay	6 (6.0)	2
100	AstraZeneca discontinued clinical candidates	AstraZeneca	• P. falciparum NF54

SJCRH, St Jude’s Children’s Research Hospital; FDA, Food and Drug Administration; GSK, GlaxoSmithKline; HTS, high-throughput screening; DAPI, 4′,6-diamidino-2-phenylindole.
*Two additional compounds were sourced for in vivo testing, one each from Novartis and Cephalon Inc. In vivo testing was performed only on those compounds that had an acceptable clinical toxicity/safety/pharmacokinetic profile (or no clinical data). Except for AstraZeneca compounds, which were tested in house, all in vivo testing was performed by GlaxoSmithKline.

ISSN: 1475-2875