Identification of inhibitors of the Leishmania cdc2-related protein kinase CRK3

Cleghorn, L.A.T. et al. (2011) Identification of inhibitors of the Leishmania cdc2-related protein kinase CRK3. ChemMedChem, 6(12), pp. 2214-2224. (doi: 10.1002/cmdc.201100344)

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Publisher's URL: http://dx.doi.org/10.1002/cmdc.201100344

Abstract

New drugs are urgently needed for the treatment of tropical parasitic diseases such as leishmaniasis and human African trypanosomiasis (HAT). This work involved a high-throughput screen of a focussed kinase set of similar to 3400 compounds to identify potent and parasite-selective inhibitors of an enzymatic <i>Leishmania</i> CRK3-cyclin 6 complex. The aim of this study is to provide chemical validation that <i>Leishmania</i> CRK3-CYC6 is a drug target. Eight hit series were identified, of which four were followed up. The optimisation of these series using classical SAR studies afforded low-nanomolar CRK3 inhibitors with significant selectivity over the closely related human cyclin dependent kinase CDK2.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mottram, Professor Jeremy
Authors: Cleghorn, L.A.T., Woodland, A., Collie, I.T., Torrie, L.S., Norcross, N., Luksch, T., Mpamhanga, C., Walker, R.G., Mottram, J.C., Brenk, R., Frearson, J.A., Gilbert, I.H., and Wyatt, P.G.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:ChemMedChem
ISSN:1860-7179
ISSN (Online):1860-7187

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