Investigation of 3 Industry-Wide Applied Storage Conditions for Compound Libraries

@article{Ilouga2007InvestigationO3,
  title={Investigation of 3 Industry-Wide Applied Storage Conditions for Compound Libraries},
  author={Pierre E Ilouga and Dirk Winkler and Christiane Kirchhoff and Bernd Schierholz and Julian W{\"o}lcke},
  journal={Journal of Biomolecular Screening},
  year={2007},
  volume={12},
  pages={21 - 32}
}
The appropriate storage conditions for a compound file are a crucial factor for the success of drug discovery projects. In this study, 778 highly diverse compounds dissolved in 100% DMSO were stored under 3 industry-wide accepted storage conditions, and the compound integrity was monitored for a period of 6 months. The storage conditions selected were (1) under argon at +15 °C, (2) under argon at -20 °C, and (3) under ambient atmosphere at -20 °C. Each sample was assessed every 4 weeks by… 

Figures and Tables from this paper

Best Practices in Compound Management for Preserving Compound Integrity and Accurately Providing Samples for Assays

A series of experiments evaluating the effects of processing compounds with volatile solvents, storage conditions that can induce freeze/thaw cycles, and the delivery of compounds were performed and how they affect compound integrity and the accuracy of compound management processes are presented.

Stability of Screening Compounds in Wet DMSO

The authors monitor the purity of a subset of 1404 compounds from ongoing medicinal chemistry projects and demonstrate that 85% of the compounds were stable in wet DMSO over a 2-year period at 4 °C, validating the storage concept developed at Novartis as a pragmatic approach.

Stability Through the Ages: The GSK Experience

GlaxoSmithKline has undertaken stability experiments over more than a decade, initially to support the implementation of new automated liquid stores (ALS) and, subsequently, to enhance storage and use of compounds in solution through an understanding of compound degradation under storage and assay conditions.

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

Of all the factors investigated, initial purity was the only one that had a clear effect on stability, and none of the other parameters investigated had a statistically significant effect on Stability.

Maintaining a High-Quality Screening Collection: The GSK Experience

This article presents how QC data can be mined using a data-driven clustering algorithm to identify chemical substructures likely to cause degradation in DMSO and suggests an efficient, targeted approach to compound collection clean-up initiatives.

Characterization of Short-Term Temperature, Exposure, and Solubilization Effects on Library Compound Quality

Temperature had a significant impact on compound concentration, and the effects due to exposure cycles were minimal; the acoustic solubilization protocol also increased the number of compounds at the target concentration with no impact on overall purity, leading to a potential for increased storage times at frozen temperatures.

Monitoring Compound Integrity With Cytochrome P450 Assays and qHTS

The authors describe how room temperature storage of a 1120-member compound library prepared in either DMSO or in a hydrated-DMSO/water (67/33) mixture affects the reproducibility of potency values

Review: Advances in Improving the Quality and Flexibility of Compound Management

In recent years, the focus in CM has been increasingly in compound quality and increased flexibility of the process, as opposed to number of compounds dispensed and speed of dispensing, which were standard metrics and indicators used not so long ago.

Can archival science add value to chemical compound library management?

A review of the four dimensions – create, capture, organise and pluralise – of the Records Continuum Model has been employed to address some of the issues associated with the management of large chemical compound libraries.

Working with small molecules: preparing and storing stock solutions and determination of kinetic solubility.

Nephelometry is introduced as a fast method to determine the kinetic solubility of a compound.

References

SHOWING 1-10 OF 19 REFERENCES

Studies on Repository Compound Stability in DMSO under Various Conditions

The chemical stability of repository compounds is affected by various environmental conditions during long-term storage, and results indicate no significant compound loss after 11 freeze/thaw cycles.

The Effect of Room-Temperature Storage on the Stability of Compounds in DMSO

An acceptable limit for compound loss and corresponding maximum storage time for samples in DMSO can be determined based on these results.

The Effect of Freeze/Thaw Cycles on the Stability of Compounds in DMSO

A diverse set of 320 compounds from the Procter & Gamble Pharmaceuticals organic compound repository was prepared as 20-mM DMSO solutions and stored at 4°C under argon in pressurized canisters to simulate a low-humidity environment to determine the maximum number of freeze/thaw cycles that can be achieved while maintaining acceptable compound integrity.

High throughput sonication: evaluation for compound solubilization.

It is reported here that efficient compound dissolution is possible even in 384 well format by the use of in-well plate-based sonication, and it is demonstrated that precipitation of compound from DMSO stock solutions is synergistically enhanced by water uptake into D MSO compound stock solutions as well as by increasing the number of freeze thaw cycles.

Phase Diagram for the System Water–Dimethylsulphoxide

Measurements indicate that the system water– DMSO can, in all proportions, be crystallized completely, and that, in certain conditions, a stable hydrate (DMSO.3H2O) is formed.

Target-oriented and diversity-oriented organic synthesis in drug discovery.

Several synthetic planning principles for diversity-oriented synthesis and their role in the drug discovery process are presented in this review.

Applied statistics in the pharmaceutical industry : with case studies using S-Plus

Analysis of Large Designed Experiments Using Trellis Graphics and Tree-Based Regression and S-PLUS Programming for the Evaluation of the Decimal Reduction Time of a Sterilization Process in Pharmaceutical Production and Acceptance Sampling Using S- PLUS.

What is molecular diversity?

This book addresses generation of molecular diversity, application of diversity for screening against alternative targets of all types, analysis of results and their application in various scientific disciplines.

Numerical recipes in C

The Diskette v 2.06, 3.5''[1.44M] for IBM PC, PS/2 and compatibles [DOS] Reference Record created on 2004-09-07, modified on 2016-08-08.

Mixed-Effects Models in S and S-PLUS

Linear Mixed-Effects * Theory and Computational Methods for LME Models * Structure of Grouped Data * Fitting LME Models * Extending the Basic LME Model * Nonlinear Mixed-Effects * Theory and