Table 3. Criteria for Target Prioritization.

tier 1 target assessment		ranking
Genetic validation	Conditional knockout. Target vulnerability upon conditional knock-down	high
	Essential in genome-wide saturation mutagenesis in P. falciparum and/or homologous recombination-mediated knockout screen in P. berghei	medium
Chemical validation	Compound-target pair established rigorously	high
	Good correlation between enzyme and cell activity over 3 log units for a compound series	medium
Resistance potential	Irresistible—no resistance found in selections	high
	MIR 8–9 and no cross resistance with any drug in clinical use or development	medium
	6 < MIR < 8 and no cross resistance with any drug in clinical use or development	low
	MIR ≤ 6 and an EC50 shift > 10-fold; or evidence of high-grade resistance-conferring SNPs in field isolates; or enzyme not conserved across Plasmodium species	STOP

tier 2 target assessment		score
Druggability	Identification of small molecule inhibitors with drug-like physicochemical properties	high
	Computational analysis of the crystal structure or a high quality homology model	medium
TPP/TCP fit	Must be active against at least two life cycle stages at similar concentrations OR blood stage asexual stages with a fast rate of kill	STOP/GO
Toxicity	No close orthologue present; selective small molecule inhibitors for parasite enzyme vs human enzyme	high
Novelty/prior information	Previous work has indicated issues with chemistry, but potential way forward using new information/chemistry	medium
	Previous work has indicated that drug-like inhibitors with in vivo activity can be generated and compound(s) in late stage development; potential for back up compound.	low
Assay readiness	Protein expressed and biochemical assay developed for this protein or a close orthologue	high
	No P. falciparum protein expressed, but (evidence for) assay for orthologue or reporter cell assay developed	medium
Structural information	Structure of target protein and cocrystal structures with ligands; evidence that it can be soaked	high
	Structure of target protein, but no complex; close orthologue with structures; potential for chimeras	medium