C. M. Richardson et al. / Bioorg. Med. Chem. Lett. 17 (2007) 3880–3885
3885
18. Berman, H. M.; Westbrook, J.; Feng, Z.; Gilliland, G.;
Bhat, T. N.; Weissig, H.; Shindyalov, I. N.; Bourne, P. E.
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In summary, virtual screening against CDK2 identified a
submicromolar inhibitor, with a distinctive binding
mode and selectivity over a number of other kinases.
A structure-guided lead scoping exercise led to the iden-
tification of a 30 nM CDK2 inhibitor 13 with selectivity
over GSK-3b of over 14-fold. Crystal structures were
obtained for a number of compounds of interest, and
provided important validation of the unusual binding
mode and support for optimization. It was also ob-
served that the 2-imino-thiazolidin-4-one moiety is able
to interact more classically with the kinase binding mo-
tif, as was verified by the crystal structure of CDK2 in
complex with a smaller ligand, which also contains this
functionality.
´
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Acknowledgment
The authors acknowledge James Davidson for addi-
tional proof reading.
27. Garmendia-Doval, A. B.; Morley, S. D.; Juhos, S. In
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