SCRIPDB: a portal for easy access to syntheses, chemicals and reactions in patents

Heifets, Abraham; Jurišica, Igor

doi:10.1093/nar/gkr919

Cited by 18 publications

(14 citation statements)

References 28 publications

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“…These have recently been joined by new public resources that include chemical structures extracted from patents. These include extractions from US patents in SCRIPDB [19], the deposition from IBM of structures from pre-2000 patents into PubChem [20], selected European patent structures added to PubChem by the SLING Consortium [21], and the recent release of SureChemOpen [22].…”

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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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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“…Nearly 75% of the +500 thousand substances with “invalid organic-only” atom types are from three PubChem contributors: SCRIPDB [179,784 (33.6%)] [ 68 , 69 ], IBM [131,014 (24.5%)] [ 70 ], and ChemSpider [85,894 (16.1%)] [ 71 ]. Examples from SCRIPDB are depicted in Figs.…”

Section: Resultsmentioning

confidence: 99%

PubChem atom environments

2015

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BackgroundAtom environments and fragments find wide-spread use in chemical information and cheminformatics. They are the basis of prediction models, an integral part in similarity searching, and employed in structure search techniques. Most of these methods were developed and evaluated on the relatively small sets of chemical structures available at the time. An analysis of fragment distributions representative of most known chemical structures was published in the 1970s using the Chemical Abstracts Service data system. More recently, advances in automated synthesis of chemicals allow millions of chemicals to be synthesized by a single organization. In addition, open chemical databases are readily available containing tens of millions of chemical structures from a multitude of data sources, including chemical vendors, patents, and the scientific literature, making it possible for scientists to readily access most known chemical structures. With this availability of information, one can now address interesting questions, such as: what chemical fragments are known today? How do these fragments compare to earlier studies? How unique are chemical fragments found in chemical structures?ResultsFor our analysis, after hydrogen suppression, atoms were characterized by atomic number, formal charge, implicit hydrogen count, explicit degree (number of neighbors), valence (bond order sum), and aromaticity. Bonds were differentiated as single, double, triple or aromatic bonds. Atom environments were created in a circular manner focused on a central atom with radii from 0 (atom types) up to 3 (representative of ECFP_6 fragments). In total, combining atom types and atom environments that include up to three spheres of nearest neighbors, our investigation identified 28,462,319 unique fragments in the 46 million structures found in the PubChem Compound database as of January 2013. We could identify several factors inflating the number of environments involving transition metals, with many seemingly due to erroneous interpretation of structures from patent data. Compared to fragmentation statistics published 40 years ago, the exponential growth in chemistry is mirrored in a nearly eightfold increase in the number of unique chemical fragments; however, this result is clearly an upper bound estimate as earlier studies employed structure sampling approaches and this study shows that a relatively high rate of atom fragments are found in only a single chemical structure (singletons). In addition, the percentage of singletons grows as the size of the chemical fragment is increased.ConclusionsThe observed growth of the numbers of unique fragments over time suggests that many chemically possible connections of atom types to larger fragments have yet to be explored by chemists. A dramatic drop in the relative rate of increase of atom environments from smaller to larger fragments shows that larger fragments mainly consist of diverse combinations of a limited subset of smaller fragments. This is further supported by the observed concomitant ...

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“…Heifets and Jurisica built SCRIPDB (a chemical structure database) used USPTO bulk download from Google servers to retrieve patents available since 2010 [23] . Papadatos et al used patent data from USPTO, EPO and WIPO, together with titles and abstracts from the JPO (processed in the XML format) to build SureChEMBL, a database with compound's structures.…”

Section: Figmentioning

confidence: 99%