Table 4 |.

Approaches to antimalarial target discovery

	No tool compound	Tool compound available
Methods	Genomic and homology methods	In vitro evolution and whole-genome analysis	Proteomic methods	Overexpression or knockdown libraries	In silico methods
Advantages	Does not involve chemical tool compound; can give large numbers of candidate targets (but possible false positives)	Has led to dozens of targets in malaria; does not require many upfront biological tools	Has worked a few times for Plasmodium; does not require many upfront biological tools	Has worked well in other species	Lower cost
Disadvantages	Extensive downstream work required; high risk of failure	Can be time-consuming; can give resistance genes; might not work for all compounds	Might not work for all compounds; might give false positives; might miss important proteins	Requires development of biological tools; can give resistance genes; might give false positives	Limited accuracy; not good for compounds with novel mechanisms; difficult to test hypotheses; extensive downstream work required
Examples of targets	GCN5, GGPPS, DHODH	PI4K, KRS, YRS, FRS, PRS, CytB, EF2, ACS, PfATP4, GGPPS, YRS DHODH, DHFR-TS	PI4K, PKG	None to date, but good examples from other species	DHFR, DHODH, CytB