Abstract：
:CDC25 phosphatases play critical roles in cell cycle regulation and are attractive targets for anticancer therapies. Several small non-peptide molecules are known to inhibit CDC25, but many of them appear to form a covalent bond with the enzyme or act through oxidation of the thiolate group of the catalytic cysteine. Structure-based virtual ligand screening computations were performed with FRED, Surflex, and LigandFit, a compound collection of over 310,000 druglike molecules and the crystal structure of CDC25B in order to identify novel classes of ligands. In vitro experiments carried out on a selected list of 1500 molecules led to the discovery of 99 compounds able to inhibit CDC25B activity at 100 microM. Further docking computations were applied, allowing us to propose a binding mode for the most potent molecule (IC50 = 13 microM). Our best compounds represent promising new classes of CDC25 inhibitors that also exhibit antiproliferative properties.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Montes M,Braud E,Miteva MA,Goddard ML,Mondésert O,Kolb S,Brun MP,Ducommun B,Garbay C,Villoutreix BOdoi
10.1021/ci700313esubject
Has Abstractpub_date
2008-01-01 00:00:00pages
157-65issue
1eissn
1549-9596issn
1549-960Xjournal_volume
48pub_type
杂志文章abstract：:Generalization of an earlier algorithm has led to the development of new local structural alignment algorithms for prediction of protein-protein binding sites. The algorithms use maximum cliques on protein graphs to define structurally similar protein regions. The search for structural neighbors in the new algorithms ...
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