Defining and maintaining a high quality screening collection: the GSK experience

Lane, Stephen; Eggleston, Drake S.; Brinded, Keith A.; Hollerton, J. C.; Taylor, N; Readshaw, Simon A.

doi:10.1016/s1359-6446(05)03730-x

Cited by 42 publications

(28 citation statements)

References 2 publications

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“…These numbers are consistent with data published on the quality of large compound collections. Among others, Lane et al 3 concluded that these numbers are typical for large, historical compound collections assembled over the same period of time. It is noteworthy, though (and corroborates the result of our study), that the adoption of this pragmatic concept that put no emphasis on storage in dry DMSO did not result in a solution collection of detectable lower quality.…”

Section: Quality Of the Study Set Versus Quality Of The Active Screenmentioning

confidence: 99%

“…These investigations help library managers to establish mid-term strategies for a progressive enhancement of the quality of their collections. In a different strategy, Lane et al 3 described the project implemented at GlaxoSmithKline that achieved a radical cleanup of the 1.4 million repository compounds by analyzing the entire collection over 18 months. Overall, 61% of compounds were found to pass the first selection criterion (UV purity >80%), and this pass rate was found to be consistent for both heritage collections, although their composition and storage conditions were fairly different.…”

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confidence: 99%

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Stability of Screening Compounds in Wet DMSO

Engeloch¹,

Schopfer²,

Muckenschnabel³

et al. 2008

SLAS Discovery

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The impact of storage conditions on compound stability and compound solubility has been debated intensely over the past 5 years. At Novartis, the authors decided to opt for a storage concept that can be considered controversial because they are using a DMSO/water (90/10) mixture as standard solvent. To assess the effect of water in DMSO stocks on compound stability, the authors monitored the purity of a subset of 1404 compounds from ongoing medicinal chemistry projects over several months. The study demonstrated that 85% of the compounds were stable in wet DMSO over a 2-year period at 4 °C. This result validates the storage concept developed at Novartis as a pragmatic approach that takes advantage of the benefits of DMSO/water mixtures while mediating the disadvantages. In addition, the authors describe how purity data collected over the course of the chemical validation of high-throughput screening actives are used to improve the analytical quality of the Novartis screening deck. (Journal of Biomolecular Screening 2008:999-1006

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Section: Quality Of the Study Set Versus Quality Of The Active Screenmentioning

confidence: 99%

mentioning

confidence: 99%

Stability of Screening Compounds in Wet DMSO

Engeloch¹,

Schopfer²,

Muckenschnabel³

et al. 2008

SLAS Discovery

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“…At this stage, a quality control (QC) check of the sample would be made by on--line LC--UV--ELSD--MS (liquid chromatographyultraviolet spectroscopy -evaporative light scattering -mass spectrometry) [35] so that the purity (UV profile), identity (MS) and quantity (ELSD) of the material in the sample could be confirmed. Other organisations have taken the approach of performing QC checks on the entire screening file but this is a major undertaking [38]. Failure to perform QC checks at the hit stage will lead to resource wastage downstream, chasing compound activity that vanishes.…”

Section: Challenges For Academic Drug Discoverymentioning

confidence: 99%

Academic drug discovery: current status and prospects

Everett¹

2015

Expert Opinion on Drug Discovery

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Introduction. The contraction in pharmaceutical drug discovery operations in the past decade has been counter--balanced by a significant rise in the number of academic drug discovery groups. In addition, pharmaceutical companies that used to operate in completely independent, vertically--integrated operations for drug discovery are now collaborating more with each other, and with academic groups. We are in a new era of drug discovery.Areas Covered. This review provides an overview of the current status of academic drug discovery groups, their achievements and the challenges they face,, together with perspectives on ways to achieve improved outcomes.Expert Opinion. Academic groups have made important contributions to drug discovery, from its earliest days and continue to do so today. However, modern drug discovery and development is exceedingly complex, and has high failure rates, principally because human biology is complex and poorly understood.

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“…In a pursuit of the ''pure and sure'' ideal, some research organizations undertook the enormous task of analysing their entire screening collections. In the case of the combined heritage collections of SmithKline Beecham and GlaxoWellcome at the time of their merger, the new collection contained well over a million compounds [11]. Analysis of the whole was achieved using custom-built HPLC systems equipped with a 384-well-plate autosampler and a sequence of diode array (DAD), evaporative light scattering (ELSD), and mass spectrometry (positive-and negative-ion electrospray) detectors.…”

Section: Sample Purity and Identitymentioning

confidence: 99%