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Just-in-Time Purification: An Effective Solution for Cherry-Picking and Purifying Active Compounds from Large Legacy Libraries

Genomics Institute of the Novartis Research Foundation, San Diego, California

Michael Kwok

Genomics Institute of the Novartis Research Foundation, San Diego, California

James J. Hanlon

Genomics Institute of the Novartis Research Foundation, San Diego, California

Tracy A. Spalding

Genomics Institute of the Novartis Research Foundation, San Diego, California

Karen Wolff

Genomics Institute of the Novartis Research Foundation, San Diego, California

Hong Yin

Genomics Institute of the Novartis Research Foundation, San Diego, California

Kelli Kuhen

Genomics Institute of the Novartis Research Foundation, San Diego, California

Kimberly Sasher

Genomics Institute of the Novartis Research Foundation, San Diego, California

Paul Calvin

Genomics Institute of the Novartis Research Foundation, San Diego, California

Shumei Jiang

Genomics Institute of the Novartis Research Foundation, San Diego, California

Yingyao Zhou

Genomics Institute of the Novartis Research Foundation, San Diego, California

John J. Isbell

Genomics Institute of the Novartis Research Foundation, San Diego, California

Many companies possess a compound collection consisting of purified compounds and of unpurified products from combinatorial libraries. Using commercial and proprietary compounds as examples, this report provides clear examples of the significant impact purification can have on the activity observed for a compound and highlights the need to retest the purified compounds prior to creating structure-activity relationships. Crude mixtures made with commercial compounds led to an increase in the number of false positives in the SXR-GAL4 assay as compared with their pure and purified counterparts. An examination of proprietary compounds in an HIV assay resulted in the purification of 61 active crude synthetic mixtures. Of these 61 compounds, 32 were 5-fold less active and 2 were 5-fold more active after purification. This report details a semiautomated process developed and implemented for cherry-picking, tracking, and selectively purifying compounds found active in high-throughput screening campaigns.

Key Words: purification • false positives • high-throughput screening • purification • SXR • HIV

This version was published on December 1, 2006

Journal of Biomolecular Screening, Vol. 11, No. 8, 933-939 (2006)
DOI: 10.1177/1087057106294289


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