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Article

Rational drug design approach for overcoming drug resistance: application to pyrimethamine resistance in malaria.

Journal of medicinal chemistry - 23 Apr 1998

McKie J H, Douglas K T, Chan C, Roser S A, Yates R, Read M, Hyde J E, Dascombe M J, Yuthavong Y, Sirawaraporn W

Abstract excerpt

Pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase (DHFR-TS). Resistance in the most important human parasite, Plasmodium falciparum, initially results from an S108N mutation in the DHFR domain, with additional mutation (most commonly C59R or N51I or both) imparting much greater resistance. From a homology model of the 3-D structure of DHFR-TS, rational drug design...

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PMID: 9554869
DOI: 10.1021/jm970845u

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DHFR

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-08.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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