4.4 Article

Current and emerging target identification methods for novel antimalarials

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ELSEVIER SCI LTD
DOI: 10.1016/j.ijpddr.2022.11.001

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Target identification; Plasmodium falciparum; Antimalarial; CETSA; Chemoproteomics

资金

  1. NHMRC [APP1163235, APP1148700]

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This review provides an overview of various techniques for antimalarial target identification, including in vitro resistance generation, metabolomics screening, chemoproteomic approaches, and biophysical assays. The strengths and weaknesses of these methods are compared, and their applications in antimalarial research are analyzed.
New antimalarial compounds with novel mechanisms of action are urgently needed to combat the recent rise in antimalarial drug resistance. Phenotypic high-throughput screens have proven to be a successful method for identifying new compounds, however, do not provide mechanistic information about the molecular target(s) responsible for antimalarial action. Current and emerging target identification methods such as in vitro resistance generation, metabolomics screening, chemoproteomic approaches and biophysical assays measuring protein stability across the whole proteome have successfully identified novel drug targets. This review provides an overview of these techniques, comparing their strengths and weaknesses and how they can be utilised for antimalarial target identification.

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