title: Just-in-time purification: an effective solution for cherry-picking and purifying active compounds from large legacy libraries.
abstract: 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.
authors.affiliation: Genomics Institute of the Novartis Research Foundation, San Diego, California 92121, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Guintu
authors.forename: Michael
authors.initials: M
authors.lastname: Kwok
authors.forename: James J
authors.initials: JJ
authors.lastname: Hanlon
authors.forename: Tracy A
authors.initials: TA
authors.lastname: Spalding
authors.forename: Karen
authors.initials: K
authors.lastname: Wolff
authors.forename: Hong
authors.initials: H
authors.lastname: Yin
authors.forename: Kelli
authors.initials: K
authors.lastname: Kuhen
authors.forename: Kimberly
authors.initials: K
authors.lastname: Sasher
authors.forename: Paul
authors.initials: P
authors.lastname: Calvin
authors.forename: Shumei
authors.initials: S
authors.lastname: Jiang
authors.forename: Yingyao
authors.initials: Y
authors.lastname: Zhou
authors.forename: John J
authors.initials: JJ
authors.lastname: Isbell
mesh_terms: D002853:Chromatography, Liquid; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005189:False Positive Reactions; D013058:Mass Spectrometry; D013048:Specimen Handling