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@article{Craven:2018:10.1002/ange.201711825,
author = {Craven, GB and Affron, DP and Allen, CE and Matthies, S and Greener, JG and Morgan, RML and Tate, EW and Armstrong, A and Mann, DJ},
doi = {10.1002/ange.201711825},
journal = {Angewandte Chemie},
pages = {5355--5359},
title = {High-throughput kinetic analysis for target-directed covalent ligand discovery},
url = {http://dx.doi.org/10.1002/ange.201711825},
volume = {130},
year = {2018}
}

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TY  - JOUR
AB  - Cysteinereactive small molecules are used as chemical probes of biological systems and as medicines. Identifying highquality covalent ligands requires comprehensive kinetic analysis to distinguish selective binders from panreactive compounds. Quantitative irreversible tethering (qIT), a general method for screening cysteinereactive small molecules based upon the maximization of kinetic selectivity, is described. This method was applied prospectively to discover covalent fragments that target the clinically important cell cycle regulator Cdk2. Crystal structures of the inhibitor complexes validate the approach and guide further optimization. The power of this technique is highlighted by the identification of a Cdk2selective allosteric (type IV) kinase inhibitor whose novel modeofaction could be exploited therapeutically.
AU  - Craven,GB
AU  - Affron,DP
AU  - Allen,CE
AU  - Matthies,S
AU  - Greener,JG
AU  - Morgan,RML
AU  - Tate,EW
AU  - Armstrong,A
AU  - Mann,DJ
DO  - 10.1002/ange.201711825
EP  - 5359
PY  - 2018///
SN  - 0044-8249
SP  - 5355
TI  - High-throughput kinetic analysis for target-directed covalent ligand discovery
T2  - Angewandte Chemie
UR  - http://dx.doi.org/10.1002/ange.201711825
UR  - https://onlinelibrary.wiley.com/doi/full/10.1002/ange.201711825
UR  - http://hdl.handle.net/10044/1/73982
VL  - 130
ER  -

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