Sean Ekins

Sean Ekins is a British pharmacologist and expert in the fields of ADME/Tox, computational toxicology and cheminformatics at Collaborations in Chemistry, a division of corporate communications firm Collaborations in Communications. He is also the editor of four books and a book series for John Wiley & Sons.

Biography

Sean Ekins was born in Cleethorpes, England, on 2 March 1970 to John Ekins and Elsie May Ekins. He grew up in Grimsby. Ekins attended Edward Street Primary and Middle School followed by Havelock School. Ekins then earned his HND Science (Applied Biology from Nottingham Trent University (formerly Polytechnic, 1988–1991), graduating in 1991, with a sandwich year (1989–1990) at the pharmaceutical company Servier in Fulmer, UK where his interest in drug discovery was established. Ekins then earned his M.Sc. in Clinical Pharmacology (1991–1992) at the University of Aberdeen with a dissertation entitled “Speculations on the relative roles of cytochrome P450 and flavin containing monooxygenase in the metabolism of S12363”^[1] he then earned a Ph.D. in clinical pharmacology, at the University of Aberdeen in 1996, funded by Servier, and wrote a thesis entitled “Maintenance and cryopreservation of xenobiotic metabolism in precision-cut liver slices. Evaluation of an alternative in vitro model to isolated hepatocytes”. During his PhD he developed an interest in predicting drug-drug interactions computationally as an alternative to using animal models.

From 1996-1998 Ekins continued his research as a Postdoc at Eli Lilly and Company laboratories characterizing the little-known CYP2B6 and applied computational methods to this enzyme. He collected drug-drug interaction Ki data for other P450s and generated pharmacophores. He created test sets to test the models, that were ultimately published.^{[2][3][4][5][6]} He published seminal ideas on how such models could be used to profile libraries of compounds for predicted drug-drug interactions.^[7][8]

In late 1998 Ekins joined Pfizer and continued his interest in predicting drug-drug interactions and ADME properties. In 1999 he moved to Lilly to build a predictive ADME/Tox group. Between 1999 and late 2001 he generated pharmacophores and statistical models for various proteins including P-glycoprotein,^{[9][10][11][12]} PXR^[13] and enzymes.^[14][15]

In December 2001 he started work for a start-up company, Concurrent Pharmaceuticals (now Vitae Pharmaceuticals) as the Associate Director, Computational Drug Discovery. He was responsible for developing computational models for ADME/Tox and targets of interest. During this time he developed an interest in the polypharmacology of ADME/Tox proteins. In 2004 he joined GeneGo (now owned by Thomson Reuters) as Vice President, Computational Biology and developed the MetaDrug product (patent pending).^{[16][17][18][19]}

In 2005 he earned his D.Sc. in Science from the University of Aberdeen with a thesis entitled “Computational and in vitro models for predicting drug interactions in humans”.

Since 2006 Ekins has consulted for several companies including on pharmacoeconomics and performing research on Tuberculosis Drug Discovery for Collaborative Drug Discovery.^[20][21][22]

Ekins has also carried out independent research and collaborative research on topics including pharmacophores for drug transporters, cheminformatics for predicting immunoassay cross reactivity, models for studying nuclear receptor-ligand co-evolution, computational models for PXR agonists and antagonists as well as analyses of large datasets and crowdsourcing data.

Making Pharmaceutical Data Open

In 2010 Sean Ekins was the co-author on seminal papers around data sharing and making pharmaceutical data more open that suggest:

1. the long overdue need for making preclinical ADME/Tox data precompetitive ^[23]

2. how crowdsourcing could be used in the pharmaceutical industry ^[24]

3. how computational models for pharmacoeconomics could be shared by the scientific community^[25]

4. what tools are still needed in cheminformatics and how methods for model sharing will be important^[26]

5. How pharmaceutical companies could use open source molecular descriptors and algorithms which would facilitate computational model sharing with the academic and neglected disease community^[27]

This work is important because it is the first time that anyone has proposed a broad array of approaches to make preclinical and postmarketing data and models available as well as demonstrate the feasibility of such approaches. Ekins has served on the advisory group for ChemSpider and provided an array of pharmaceutical data sets to the database to make it available to the community.

Tuberculosis and Malaria Research

While working for Collaborative Drug Discovery, (funded by the Bill and Melinda Gates Foundation) he analyzed data provided to the public domain by the pharmaceutical industry. Specifically this was malaria screening data from GlaxoSmithKline for over 13,000 compounds. As a result of this work an important caution was provided to the scientific community in accepting such data at face value.^[28] These data were compared to other malaria and tuberculosis data.^[29]

In addition he has provided analyses of very large libraries of tuberculosis data which highlight important physicochemical properties,.^[30][31]

Ekins has highlighted gaps in TB research, specifically in how cheminformatics and other computational tools could be integrated to improve efficiency^[32] and provided examples of how computational methods can be used to assist in screening for compounds active against TB^[33]

In February 2011 Ekins began participating in the MM4TB project as part of Collaborative Drug Discovery ^[34] lead by Professor Stewart Cole.^[35]

Science Mobile Applications

Ekins co-developed a Wiki with Antony John Williams called Science Mobile Applications^[36] launched June 21, 2011.^[37] Initially this grew out of a desire to track chemistry Apps^[38] (for a paper submitted) and then Apps for science in the chemistry classroom.^[39]

Database quality

Using their respective blogs, Ekins and Antony Williams alerted the scientific community within days of the release of the NCGC NPC browser ^[40] that there were significant errors in molecule structures. These observations were later published as an editorial in Drug Discovery Today.^[41]

Editorships

Ekins has edited or co-edited 4 books for Wiley including: Computer Applications in Pharmaceutical Research and Development (2006), Computational Toxicology: Risk Assessment For Pharmaceutical and Environmental Chemicals(1007), Drug Efficacy, Safety, and Biologics Discovery(2009) and Collaborative Computational Technologies for Biomedical Research (2011) All the books have an underlying connection with computational technologies and their application for pharmaceutical R & D.

Ekins is the Editor of Expert Reviews for the journal Pharmaceutical Research,^[42][43] a Springer Journal. He solicits reviews, commentaries and perspectives for the field of pharmaceutical research. He is on the editorial board for Drug Metabolism and Disposition,^[44] Journal of Pharmacological and Toxicological Methods,^[45] Mutation Research - Reviews,^[46] and Drug Discovery Today ^[47]

Patents

Ekins is inventor on two issued US patents,^[48] and ^[49]

References

External links

• Sean Ekins LinkedIn Profile
• Collaborations in Chemistry
• Sean Ekins Presentations
• Sean Ekins Blog
• User profile on Google scholar