Quality Assessment and Analysis of Biogen Idec Compound Library

Abstract

A subset of the compound repository for lead identification at Biogen Idec was characterized for its chemical stability over a 3-year period. Compounds were stored at 4 degrees C as 10 mM DMSO stocks, and a small subset of compounds was stored as lyophilized dry films. Compound integrity of 470 discrete compounds (Compound Set I) and 1917 combinatorial chemistry-derived compounds (Compound Set II) was evaluated by liquid chromatography/mass spectrometry from the time of acquisition into the library collection and after 3 years of storage. Loss of compound integrity over the 3 years of storage was observed across the 2 subsets tested. Of Compound Set I, 63% of samples retained > 80% purity, whereas 57% of samples from Compound Set II had purity greater than 60%. The stability of the lyophilized samples was superior to the samples stored as DMSO solution. Although storage at 4 degrees C as DMSO solution was adequate for the majority of compounds, the authors observed and quantified the level of degradation within the compound collection. Their study provides general insight into compound storage and selection of library subsets for future lead identification activities.

High Throughput Screening in the Twenty-First Century

“…In the rush to HTS during the early 1990s, many compound libraries were dissolved and handled under ambient conditions of temperature and humidity that inevitably led to substantial water uptake with significant effects on solubility that were only exacerbated by the frequent uncontrolled freeze/thaw cycles that these solutions endured over succeeding years of multiple reuse. It is scant wonder that LC/MS analysis of samples from several traditional HTS libraries indicated loss or degradation of 20-50% of the samples [55]. However, experiments with traditional libraries are de facto observations of ''wet'' DMSO solutions.…”

The Effect of Initial Purity on the Stability of Solutions in Storage

“…It is well accepted that the stability of solid compounds is significantly better than that of solutions. 2 Unfortunately, there are very limited options for weighing solids in small amounts (milligrams). The current limitations of solid dispensing together with the advances in liquid dispensing have led many laboratories to employ strategies that make the most use of the solution compound collection with minimal replenishment from solid.…”

Small Molecule Compound Logistics Outsourcing – Going Beyond the “Thought Experiment”

“…Rapid distribution and delivery of high quality compounds across a global pharmaceutical research organization is critically important for early evaluation and advancement of compounds within pharmaceutical discovery research [1][2][3][4]. Traditionally, compound management is highly centralized to exploit economies of scale available so that the handling millions of compound samples can be accomplished in a highly automated process [5][6][7][8][9][10][11].…”