Challenges of Connecting Chemistry to Pharmacology: Perspectives from Curating the IUPHAR/BPS Guide to PHARMACOLOGY

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2018 Aug 9

PMID 30087946

Citations 1

Authors

Christopher Southan

Joanna L Sharman

Elena Faccenda

Adam J Pawson

Simon D Harding

Jamie A Davies

Affiliations

Soon will be listed here.

Abstract

Connecting chemistry to pharmacology has been an objective of Guide to PHARMACOLOGY (GtoPdb) and its precursor the International Union of Basic and Clinical Pharmacology Database (IUPHAR-DB) since 2003. This has been achieved by populating our database with expert-curated relationships between documents, assays, quantitative results, chemical structures, their locations within the documents, and the protein targets in the assays (D-A-R-C-P). A wide range of challenges associated with this are described in this perspective, using illustrative examples from GtoPdb entries. Our selection process begins with judgments of pharmacological relevance and scientific quality. Even though we have a stringent focus for our small-data extraction, we note that assessing the quality of papers has become more difficult over the last 15 years. We discuss ambiguity issues with the resolution of authors' descriptions of A-R-C-P entities to standardized identifiers. We also describe developments that have made this somewhat easier over the same period both in the publication ecosystem and recent enhancements of our internal processes. This perspective concludes with a look at challenges for the future, including the wider capture of mechanistic nuances and possible impacts of text mining on automated entity extraction.

Citing Articles

The IUPHAR/BPS Guide to PHARMACOLOGY in 2020: extending immunopharmacology content and introducing the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY.

Armstrong J, Faccenda E, Harding S, Pawson A, Southan C, Sharman J Nucleic Acids Res. 2019; 48(D1):D1006-D1021.

PMID: 31691834 PMC: 7145572. DOI: 10.1093/nar/gkz951.

References

Zhu K, Baudhuin L, Hong G, WILLIAMS F, Cristina K, Kabarowski J . Sphingosylphosphorylcholine and lysophosphatidylcholine are ligands for the G protein-coupled receptor GPR4. J Biol Chem. 2001; 276(44):41325-35. DOI: 10.1074/jbc.M008057200. View

Noor M, Zimmerman K, Teeter K . Data sharing: how much doesn't get submitted to GenBank?. PLoS Biol. 2006; 4(7):e228. PMC: 1489975. DOI: 10.1371/journal.pbio.0040228. View

Taldone T, Zito S, Talele T . Inhibition of dipeptidyl peptidase-IV (DPP-IV) by atorvastatin. Bioorg Med Chem Lett. 2007; 18(2):479-84. DOI: 10.1016/j.bmcl.2007.11.107. View

Harmar A, Hills R, Rosser E, Jones M, Buneman O, Dunbar D . IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Nucleic Acids Res. 2008; 37(Database issue):D680-5. PMC: 2686540. DOI: 10.1093/nar/gkn728. View

Filippov I, Nicklaus M . Optical structure recognition software to recover chemical information: OSRA, an open source solution. J Chem Inf Model. 2009; 49(3):740-3. PMC: 2889020. DOI: 10.1021/ci800067r. View

Krippendorff B, Neuhaus R, Lienau P, Reichel A, Huisinga W . Mechanism-based inhibition: deriving K(I) and k(inact) directly from time-dependent IC(50) values. J Biomol Screen. 2009; 14(8):913-23. DOI: 10.1177/1087057109336751. View

Gardossi L, Poulsen P, Ballesteros A, Hult K, Svedas V, Vasic-Racki D . Guidelines for reporting of biocatalytic reactions. Trends Biotechnol. 2010; 28(4):171-80. DOI: 10.1016/j.tibtech.2010.01.001. View

. Cell line misidentification: the beginning of the end. Nat Rev Cancer. 2010; 10(6):441-8. DOI: 10.1038/nrc2852. View

Lowe D, Corbett P, Murray-Rust P, Glen R . Chemical name to structure: OPSIN, an open source solution. J Chem Inf Model. 2011; 51(3):739-53. DOI: 10.1021/ci100384d. View

10.

Southan C, Boppana K, Jagarlapudi S, Muresan S . Analysis of in vitro bioactivity data extracted from drug discovery literature and patents: Ranking 1654 human protein targets by assayed compounds and molecular scaffolds. J Cheminform. 2011; 3(1):14. PMC: 3118229. DOI: 10.1186/1758-2946-3-14. View

11.

Stevens T, Ekholm K, Granse M, Lindahl M, Kozma V, Jungar C . AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase. J Pharmacol Exp Ther. 2011; 339(1):313-20. DOI: 10.1124/jpet.111.182139. View

12.

Mullard A . Reliability of 'new drug target' claims called into question. Nat Rev Drug Discov. 2011; 10(9):643-4. DOI: 10.1038/nrd3545. View

13.

Orchard S, Al-Lazikani B, Bryant S, Clark D, Calder E, Dix I . Minimum information about a bioactive entity (MIABE). Nat Rev Drug Discov. 2011; 10(9):661-9. DOI: 10.1038/nrd3503. View

14.

Southan C, Williams A, Ekins S . Challenges and recommendations for obtaining chemical structures of industry-provided repurposing candidates. Drug Discov Today. 2012; 18(1-2):58-70. DOI: 10.1016/j.drudis.2012.11.005. View

15.

Southan C, Stracz A . Extracting and connecting chemical structures from text sources using chemicalize.org. J Cheminform. 2013; 5(1):20. PMC: 3648358. DOI: 10.1186/1758-2946-5-20. View

16.

Ekins S, Olechno J, Williams A . Dispensing processes impact apparent biological activity as determined by computational and statistical analyses. PLoS One. 2013; 8(5):e62325. PMC: 3641061. DOI: 10.1371/journal.pone.0062325. View

17.

Davenport A, Alexander S, Sharman J, Pawson A, Benson H, Monaghan A . International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol Rev. 2013; 65(3):967-86. PMC: 3698937. DOI: 10.1124/pr.112.007179. View

18.

Gilson M, Georg G, Wang S . Digital chemistry in the Journal of Medicinal Chemistry. J Med Chem. 2014; 57(4):1137. DOI: 10.1021/jm5002056. View

19.

Clark A, Bunin B, Litterman N, Schurer S, Visser U . Fast and accurate semantic annotation of bioassays exploiting a hybrid of machine learning and user confirmation. PeerJ. 2014; 2:e524. PMC: 4137659. DOI: 10.7717/peerj.524. View

20.

Orchard S, Hermjakob H . Shared resources, shared costs--leveraging biocuration resources. Database (Oxford). 2015; 2015. PMC: 4360620. DOI: 10.1093/database/bav009. View