Virtual Screening for R-Groups, including Predicted pIC50 Contributions, within Large Structural Databases, Using Topomer CoMFA

Author:

Cramer Richard D.1,Cruz Phillip1,Stahl Gunther1,Curtiss William C.1,Campbell Brian1,Masek Brian B.1,Soltanshahi Farhad1

Affiliation:

1. Tripos International, 1699 South Hanley Road, St. Louis, Missouri 63144

Publisher

American Chemical Society (ACS)

Subject

Library and Information Sciences,Computer Science Applications,General Chemical Engineering,General Chemistry

Reference40 articles.

1. ZINC − A Free Database of Commercially Available Compounds for Virtual Screening

2. Use of 3D QSAR Models for Database Screening:  A Feasibility Study

3. In order to provide at least a very rough and preliminary estimate of this important baseline value, we calculated the standard deviation of pIC50s for the primary biological assay reported within 23 recentJournal of Medicinal Chemistryarticles, limited to those from commercial organizations that mentioned a potential clinical candidate. The average value of these 23 pIC50 standard deviations was 0.89, with a standard deviation of 0.43. Not surprisingly, it was also apparent that in the majority of these publications the lead optimization goal in preparing and testing the most reported structures was no longer to improve potency in the primary assay but to maintain that potency while improving secondary properties. However such an activity will tend to depress the cumulative pIC50 standard deviation for the primary assay. So on balance we postulate a value somewhere between 1.0 and 1.3 for the standard deviation of any pIC50 that a project is actively seeking to improve.

4. Topomer CoMFA:  A Design Methodology for Rapid Lead Optimization

5. 3D-QSAR illusions

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