Beyond QSAR: Lead Hopping to Different Structures

We investigated the ability of several computer programs to detect lead hops that had been reported to result from pharmacophore searching. None of the methods identified all of these lead hops and some were not found by any program. The methods that performed the best identified different lead hops. Hence, we have deployed a lead hopping application that uses belief theory to combine the results of ROCS, Daylight, and ECFP_6 similarities.

[1]  Ramaswamy Nilakantan,et al.  Topological torsion: a new molecular descriptor for SAR applications. Comparison with other descriptors , 1987, J. Chem. Inf. Comput. Sci..

[2]  Robert P. Sheridan,et al.  Chemical Similarity Using Physiochemical Property Descriptors , 1996, J. Chem. Inf. Comput. Sci..

[3]  D R Flower,et al.  Lead generation using pharmacophore mapping and three-dimensional database searching: application to muscarinic M(3) receptor antagonists. , 1999, Journal of medicinal chemistry.

[4]  Schmid,et al.  "Scaffold-Hopping" by Topological Pharmacophore Search: A Contribution to Virtual Screening. , 1999, Angewandte Chemie.

[5]  A. Good,et al.  3-D pharmacophores in drug discovery. , 2001, Current pharmaceutical design.

[6]  Robert P Sheridan,et al.  Why do we need so many chemical similarity search methods? , 2002, Drug discovery today.

[7]  Y. Martin,et al.  Do structurally similar molecules have similar biological activity? , 2002, Journal of medicinal chemistry.

[8]  Petra Schneider,et al.  Comparison of correlation vector methods for ligand-based similarity searching , 2003, J. Comput. Aided Mol. Des..

[9]  Darren V S Green,et al.  Virtual screening of virtual libraries. , 2003, Progress in medicinal chemistry.

[10]  Myriam Witvrouw,et al.  Efficient 3D Database Screening for Novel HIV-1 IN Inhibitors , 2004, J. Chem. Inf. Model..

[11]  Robert P. Sheridan,et al.  Similarity to Molecules in the Training Set Is a Good Discriminator for Prediction Accuracy in QSAR , 2004, J. Chem. Inf. Model..

[12]  S. Prigge,et al.  A three-dimensional in silico pharmacophore model for inhibition of Plasmodium falciparum cyclin-dependent kinases and discovery of different classes of novel Pfmrk specific inhibitors. , 2004, Journal of medicinal chemistry.

[13]  G. Schneider,et al.  New Inhibitors of the Tat–TAR RNA Interaction Found with a “Fuzzy” Pharmacophore Model , 2005, Chembiochem : a European journal of chemical biology.

[14]  Gerald M. Maggiora,et al.  On Outliers and Activity Cliffs-Why QSAR Often Disappoints , 2006, J. Chem. Inf. Model..

[15]  S. Muchmore,et al.  The Use of Three‐Dimensional Shape and Electrostatic Similarity Searching in the Identification of a Melanin‐Concentrating Hormone Receptor 1 Antagonist , 2006, Chemical biology & drug design.

[16]  Robert P. Sheridan,et al.  Comparison of Topological, Shape, and Docking Methods in Virtual Screening , 2007, J. Chem. Inf. Model..

[17]  Yvonne C. Martin,et al.  Application of Belief Theory to Similarity Data Fusion for Use in Analog Searching and Lead Hopping , 2008, J. Chem. Inf. Model..