title: Target identification and validation of novel antimalarials.
abstract: It has been recognized that new antimalarials with a novel mode of action are critical to combat the continued emergence and dissemination of drug-resistant parasites that threaten the efficacy of current malaria treatments. Thus, recent high-throughput screening campaigns have been initiated using asexual intraerythrocytic stage cell-based assays of Plasmodium falciparum. These have led to the unprecedented identification of over 10,000 new antimalarial compounds. Inherently, novel compounds identified by cell-based assays will have poorly defined modes of action. While some of these compounds may have recognizable targets, the majority of cell-based hits are comprised of unique chemical scaffolds usually lacking cross-resistance with known drugs. It is likely that these novel antimalarial scaffolds will reveal new targets. A challenge for the community will be to assign these small molecules to their targets. In this article, we review methodologies to assist in the determination of a compound's mode of action.
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
authors.forename: Case
authors.initials: C
authors.lastname: McNamara
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Winzeler
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials