The Drug Discovery Portal: a resource to enhance drug discovery from academia

Clark, Rachel L.; Johnston, Blair F.; Mackay, Simon P.; Breslin, Catherine; Robertson, Murray N.; Harvey, Alan L.

doi:10.1016/j.drudis.2010.06.003

Cited by 38 publications

(17 citation statements)

References 15 publications

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“…35 , 36 The old, linear paradigm where each player's position was clearly defined has evolved into a dynamic network of non-traditional partnerships in which compounds, data, expertise and knowledge are shared. 37 , 38 The development of a repository that makes a significant volume of publicly-funded research openly-available will become increasingly valuable in an environment where the roles of industry, academia, charities and research funders in innovation are increasingly overlapping.…”

Section: Discussionmentioning

confidence: 99%

The creation and characterisation of a National Compound Collection: the Royal Society of Chemistry pilot

et al. 2016

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Section: Discussionmentioning

confidence: 99%

The creation and characterisation of a National Compound Collection: the Royal Society of Chemistry pilot

et al. 2016

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“…A recent comparison showed that 6% of compound structures exemplified in patents were also published in journal articles [11]. While the patterns described above will be typical for pharmaceutical and biotechnology companies, the situation in the academic sector differs in a number of respects [12]. Universities and research institutions are publishing increasing numbers of patents for bioactive compounds but their embargo times for publication and/or upload of screening results to open repositories, such as PubChem BioAssay, are generally shorter [13].…”

Section: Introductionmentioning

confidence: 99%

Tracking 20 Years of Compound-to-Target Output from Literature and Patents

Southan¹,

Várkonyi

Boppana³

et al. 2013

PLoS ONE

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The statistics of drug development output and declining yield of approved medicines has been the subject of many recent reviews. However, assessing research productivity that feeds development is more difficult. Here we utilise an extensive database of structure-activity relationships extracted from papers and patents. We have used this database to analyse published compounds cumulatively linked to nearly 4000 protein target identifiers from multiple species over the last 20 years. The compound output increases up to 2005 followed by a decline that parallels a fall in pharmaceutical patenting. Counts of protein targets have plateaued but not fallen. We extended these results by exploring compounds and targets for one large pharmaceutical company. In addition, we examined collective time course data for six individual protease targets, including average molecular weight of the compounds. We also tracked the PubMed profile of these targets to detect signals related to changes in compound output. Our results show that research compound output had decreased 35% by 2012. The major causative factor is likely to be a contraction in the global research base due to mergers and acquisitions across the pharmaceutical industry. However, this does not rule out an increasing stringency of compound quality filtration and/or patenting cost control. The number of proteins mapped to compounds on a yearly basis shows less decline, indicating the cumulative published target capacity of global research is being sustained in the region of 300 proteins for large companies. The tracking of six individual targets shows uniquely detailed patterns not discernible from cumulative snapshots. These are interpretable in terms of events related to validation and de-risking of targets that produce detectable follow-on surges in patenting. Further analysis of the type we present here can provide unique insights into the process of drug discovery based on the data it actually generates.

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“…For many years, 80% of drugs were either natural products or natural product-derived compounds. Even in the modern era, after the advent of techniques such as high-throughput screening of synthetic libraries, half of the drugs approved since 1994 are based on natural products research (3,4). Recent comprehensive reviews of natural products, or compounds inspired by natural products, indicate that more than 100 natural product compounds are currently in clinical trials.…”

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confidence: 99%

Molecular Scaffold Analysis of Natural Products Databases in the Public Domain

2012

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Natural products represent important sources of bioactive compounds in drug discovery efforts. In this work, we compiled five natural products databases available in the public domain and performed a comprehensive chemoinformatic analysis focused on the content and diversity of the scaffolds with an overview of the diversity based on molecular fingerprints. The natural products databases were compared with each other and with a set of molecules obtained from in-house combinatorial libraries, and with a general screening commercial library. It was found that publicly available natural products databases have different scaffold diversity. In contrast to the common concept that larger libraries have the largest scaffold diversity, the largest natural products collection analyzed in this work was not the most diverse. The general screening library showed, overall, the highest scaffold diversity. However, considering the most frequent scaffolds, the general reference library was the least diverse. In general, natural products databases in the public domain showed low molecule overlap. In addition to benzene and acyclic compounds, flavones, coumarins, and flavanones were identified as the most frequent molecular scaffolds across the different natural products collections. The results of this work have direct implications in the computational and experimental screening of natural product databases for drug discovery.Key words: chemoinformatics, cyclic system, molecular diversity, natural product, Shannon entropy, Traditional Chinese Medicine.Abbreviations: CSR, cumulative scaffold recovery; MACCS, Molecular ACCess System; MEQI, Molecular Equivalence Index; MOE, molecular operating environment; SE, Shannon entropy; TCM, Traditional Chinese Medicine.Received 22 June 2012, revised 18 July 2012 and accepted for publication 19 July 2012Traditionally, natural products have played a major role in drug discovery and development by providing novel chemical scaffolds, and serving as leads or drugs (1,2). For many years, 80% of drugs were either natural products or natural product-derived compounds. Even in the modern era, after the advent of techniques such as high-throughput screening of synthetic libraries, half of the drugs approved since 1994 are based on natural products research (3,4). Recent comprehensive reviews of natural products, or compounds inspired by natural products, indicate that more than 100 natural product compounds are currently in clinical trials. Natural products offer the advantage of discovering novel structural classes (5,6) because of their well-documented better coverage of chemical space relative to large synthetic compounds (7). Hence, the structural or chemical diversity of natural products can be utilized to access bioactive compounds with novel scaffolds (7-9). The inclusion of sources of natural products in drug discovery would open up more avenues for new classes of drugs (10) as well as new chemical entities, evidenced by studies that show structural or chemical complementarity between natural...

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The Drug Discovery Portal: a resource to enhance drug discovery from academia

Cited by 38 publications

References 15 publications

The creation and characterisation of a National Compound Collection: the Royal Society of Chemistry pilot

The creation and characterisation of a National Compound Collection: the Royal Society of Chemistry pilot

Tracking 20 Years of Compound-to-Target Output from Literature and Patents

Molecular Scaffold Analysis of Natural Products Databases in the Public Domain

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