Imperial College London
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Prof Ed Tate

Faculty of Natural Sciences, Department of Chemistry

GSK Chair in Chemical Biology
 
 
 
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Contact

 

+44 (0)20 7594 3752e.tate Website CV

 
 
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Assistant

 

Ms Agnes Lee +44 (0)20 7594 9852

 
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Location

 

301BMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kallemeijn:2019:10.1016/j.chembiol.2019.03.006,
author = {Kallemeijn, W and Lueg, G and Faronato, M and Hadavizadeh, K and Goya, Grocin A and Song, O-R and Howell, M and Dinnis, C and Tate, E},
doi = {10.1016/j.chembiol.2019.03.006},
journal = {Cell Chemical Biology},
pages = {892--900},
title = {Validation and invalidation of chemical probes for the human N-myristoyltransferases},
url = {http://dx.doi.org/10.1016/j.chembiol.2019.03.006},
volume = {26},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - On-target, cell-active chemical probes are of fundamental importance in both chemical and cell biology, whereas the application of poorly-characterised probes often leads to invalid conclusions.Human N-myristoyltransferase  (NMT)  has  attracted  increasing  interest  as  a  target  in  cancer  and  infectious diseases; here we report an in-depth comparison of five compounds widely applied as human NMT inhibitors, using a combination of quantitative whole-proteome N-myristoylation profiling, biochemical enzyme  assays,  cytotoxicity,  in-cell  protein  synthesis  and  cell  cycle  assays.  We  find  that N-myristoylation is unaffected by 2-hydroxymyristic acid (100 μM), D-NMAPPD (30 μM) or Tris-DBA palladium (10 μM), with the latter compounds causing cytotoxicity through mechanisms unrelated to NMT. In contrast, drug-like inhibitors IMP-366 (DDD85646) and IMP-1088 delivered complete and specific inhibition of N-myristoylation in a range of cell lines at 1 μM and 100 nM, respectively. This study enables the selection of appropriate on-target probes for future studies and suggests the need for reassessment of previous studies which used off-target compounds.
AU  - Kallemeijn,W
AU  - Lueg,G
AU  - Faronato,M
AU  - Hadavizadeh,K
AU  - Goya,Grocin A
AU  - Song,O-R
AU  - Howell,M
AU  - Dinnis,C
AU  - Tate,E
DO  - 10.1016/j.chembiol.2019.03.006
EP  - 900
PY  - 2019///
SN  - 2451-9456
SP  - 892
TI  - Validation and invalidation of chemical probes for the human N-myristoyltransferases
T2  - Cell Chemical Biology
UR  - http://dx.doi.org/10.1016/j.chembiol.2019.03.006
UR  - https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(19)30083-2?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451945619300832%3Fshowall%3Dtrue
UR  - http://hdl.handle.net/10044/1/68674
VL  - 26
ER  -
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