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Pharmaceuticals 2011, 4(9), 1236-1247; doi:10.3390/ph4091236
Article

Target Profile Prediction and Practical Evaluation of a Biginelli-Type Dihydropyrimidine Compound Library

, , , , , ,  and *
Received: 26 August 2011; in revised form: 13 September 2011 / Accepted: 16 September 2011 / Published: 20 September 2011
(This article belongs to the Special Issue Advances in Drug Design)
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Abstract: We present a self-organizing map (SOM) approach to predicting macromolecular targets for combinatorial compound libraries. The aim was to study the usefulness of the SOM in combination with a topological pharmacophore representation (CATS) for selecting biologically active compounds from a virtual combinatorial compound collection, taking the multi-component Biginelli dihydropyrimidine reaction as an example. We synthesized a candidate compound from this library, for which the SOM model suggested inhibitory activity against cyclin-dependent kinase 2 (CDK2) and other kinases. The prediction was confirmed in an in vitro panel assay comprising 48 human kinases. We conclude that the computational technique may be used for ligand-based in silico pharmacology studies, off-target prediction, and drug re-purposing, thereby complementing receptor-based approaches.
Keywords: combinatorial chemistry; drug design; in silico pharmacology; kinase inhibitor; multi-component reaction; self-organizing map combinatorial chemistry; drug design; in silico pharmacology; kinase inhibitor; multi-component reaction; self-organizing map
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Schneider, P.; Stutz, K.; Kasper, L.; Haller, S.; Reutlinger, M.; Reisen, F.; Geppert, T.; Schneider, G. Target Profile Prediction and Practical Evaluation of a Biginelli-Type Dihydropyrimidine Compound Library. Pharmaceuticals 2011, 4, 1236-1247.

AMA Style

Schneider P, Stutz K, Kasper L, Haller S, Reutlinger M, Reisen F, Geppert T, Schneider G. Target Profile Prediction and Practical Evaluation of a Biginelli-Type Dihydropyrimidine Compound Library. Pharmaceuticals. 2011; 4(9):1236-1247.

Chicago/Turabian Style

Schneider, Petra; Stutz, Katharina; Kasper, Ladina; Haller, Sarah; Reutlinger, Michael; Reisen, Felix; Geppert, Tim; Schneider, Gisbert. 2011. "Target Profile Prediction and Practical Evaluation of a Biginelli-Type Dihydropyrimidine Compound Library." Pharmaceuticals 4, no. 9: 1236-1247.



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