BibTex format
@article{Bell:2026:10.1021/acs.jmedchem.6c00914,
author = {Bell, AS and Hutton, JA and Brannigan, JA and Trainor, N and Grainger, M and Meister, S and Bonnert, R and Burrows, JN and Campo, B and Wall, RJ and Kundu, A and Wilkinson, AJ and Holder, AA and Winzeler, EA and Tewari, R and Leatherbarrow, RJ and Tate, EW},
doi = {10.1021/acs.jmedchem.6c00914},
journal = {Journal of Medicinal Chemistry},
title = {Discovery of Potent Orally Active Plasmodium <i>N</i> -Myristoyltransferase Inhibitors Using Fragment-Linking Approaches},
url = {http://dx.doi.org/10.1021/acs.jmedchem.6c00914},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - <jats:title>Abstract</jats:title> <jats:p>N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive potential drug target for parasitic infections such as malaria and leishmaniasis. Co-crystallisation of a high-throughput screening hit with P. vivax NMT identified a novel binding mode, and cooperative binding experiments with fragments identified synergistic improvements in potency and opportunities for fragment-linking. Optimisation of the torsional angle of fragment linkage through phenolic ether enabled the desired activity spectrum and selectivity profile, and examples were progressed to a mouse malaria model, resulting in the selection of IMP-1002 for further evaluation. This early lead compound was efficacious after oral administration in a SCID mouse model and is highly active against both blood- and liver-stage forms of the parasite. Finally, we discovered that highly potent human NMT inhibitors, including IMP-1088, could be generated by introducing an additional fluorine atom to further tune the torsion angle.</jats:p>
AU - Bell,AS
AU - Hutton,JA
AU - Brannigan,JA
AU - Trainor,N
AU - Grainger,M
AU - Meister,S
AU - Bonnert,R
AU - Burrows,JN
AU - Campo,B
AU - Wall,RJ
AU - Kundu,A
AU - Wilkinson,AJ
AU - Holder,AA
AU - Winzeler,EA
AU - Tewari,R
AU - Leatherbarrow,RJ
AU - Tate,EW
DO - 10.1021/acs.jmedchem.6c00914
PY - 2026///
SN - 0022-2623
TI - Discovery of Potent Orally Active Plasmodium <i>N</i> -Myristoyltransferase Inhibitors Using Fragment-Linking Approaches
T2 - Journal of Medicinal Chemistry
UR - http://dx.doi.org/10.1021/acs.jmedchem.6c00914
UR - https://doi.org/10.1021/acs.jmedchem.6c00914
ER -