The International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR): Relevance to pharmacology today and challenges for the future

S. P. Alexander¹, A. Christopoulos², A. P. Davenport³, D. Fabbro⁴, A. J. Pawson⁵, J. A. Cidlowski⁶, K. Kaibuchi⁷, Y. Kanai⁸, F. Levi-Schaffer⁹, E. H. Ohlstein¹⁰, J. A. Peters¹¹, A. Phipps¹², J. Striessnig¹³, J. A. Davies⁵, E. Faccenda⁵, S. D. Harding⁵, J. L. Sharman⁵, C. Southan⁵, S. J. Enna¹⁴, M. Spedding¹⁵. ¹School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, United Kingdom, ²Drug Discovery Biology, Monash University, Parkville, Australia, ³Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, United Kingdom, ⁴PIQUR Therapeutics, PIQUR Therapeutics, Basel, Switzerland, ⁵Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom, ⁶Department of Health and Human Services, National Institutes of Health, Research Triangle Park, ⁷Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, Japan, ⁸Department of Bio-system Pharmacology, Osaka University, Osaka, Japan, ⁹Pharmacology and Experimental Therapeutics Unit, The Hebrew University of Jerusalem, Jerusalem, Israel, ¹⁰Velicept Therapeutics, Malvern, ¹¹Neuroscience Division, University of Dundee, Dundee, United Kingdom, ¹²Pharma Research and Early Development (pRED), Roche Innovation Centre Welwyn, Welwyn Garden City, United Kingdom, ¹³Pharmacology and Toxicology, University of Innsbruck Center for Chemistry and Biomedicine, Innsbruck, Austria, ¹⁴Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, ¹⁵Spedding Research Solutions SARL, Le Vésinet, France.

Background and Aims: NC-IUPHAR was established in 1987 with the primary objective of issuing guidelines for the nomenclature and classification of receptors and ion channels. This has been extended to include all the targets of current/future prescription medicines. NC-IUPHAR has addressed many important questions, issues and controversies in pharmacology, and has overseen the development and expert-driven annotation of an authoritative and open access, global online resource, the IUPHAR/BPS Guide to PHARMACOLOGY database (GtoPdb^1,2).

Summary of work and outcomes: NC-IUPHAR disseminates its work through highly cited review articles, and via the GtoPdb website. GtoPdb provides access to expert-curated pharmacological, chemical, genetic, functional and pathophysiological data on all the known biological targets of approved and experimental drugs. It also provides an integrated educational resource with access to high quality training in the principles of basic and clinical pharmacology and techniques³. Publications are a key feature of NC-IUPHAR thanks to long-standing relationships with ASPET and BPS, for the publication of official IUPHAR nomenclature reports in Pharmacological Reviewsand state-of-field IUPHAR reviews in the British Journal of Pharmacology.

Discussion: Recent advances in our knowledge of drug targets, with increasing detail becoming available from structural approaches, has had a dramatic impact on drug discovery and pharmacology. However, drug discovery success has not advanced at the same rate as our knowledge of drug targets. This is partly due to the exponentially-increasing number of drug-related variables, including drug target polymorphisms and epigenetic phenomena, which may be crucial in disease states, but also contribute to controversy. An ongoing focus of NC-IUPHAR is to define the main variables in drug/target interactions, including all the parameters that can lead to variations in drug target function and pharmacology. NC-IUPHAR has recently expanded the development of its online resources into the arena of immunopharmacology⁴, and has plans to further extend its interests into areas including natural product research and anti-infectives.

Conclusion: The scientific community is faced with repeated reports of the lack of reproducibility of data in pre-clinical pharmacology/drug discovery. One of the core aims of GtoPdb is to provide validated, evidence-rich datasets. An ongoing goal of NC-IUPHAR is to provide further guidance on best practice in the design and analysis of experiments, leading to greater confidence in experimental outcomes.

References:

1. Southan C et al. (2016) Nucleic Acids Res. 44(D1): D1054-68.

2. IUPHAR/BPS Guide to PHARMACOLOGY database, http://www.guidetopharmacology.org/

3. IUPHAR Pharmacology Education Project, http://www.pharmacologyeducation.org/

4. IUPHAR Guide to IMMUNOPHARMACOLOGY, http://www.guidetoimmunopharmacology.org/