Perspectives

Nature Reviews Drug Discovery 11, 909-922 (December 2012) | doi:10.1038/nrd3845

OpinionReducing safety-related drug attrition: the use of in vitro pharmacological profiling

Joanne Bowes1,8, Andrew J. Brown2,8, Jacques Hamon3,8, Wolfgang Jarolimek4,8, Arun Sridhar5,8, Gareth Waldron6,8 & Steven Whitebread7,8  About the authors

Top

In vitro pharmacological profiling is increasingly being used earlier in the drug discovery process to identify undesirable off-target activity profiles that could hinder or halt the development of candidate drugs or even lead to market withdrawal if discovered after a drug is approved. Here, for the first time, the rationale, strategies and methodologies for in vitro pharmacological profiling at four major pharmaceutical companies (AstraZeneca, GlaxoSmithKline, Novartis and Pfizer) are presented and illustrated with examples of their impact on the drug discovery process. We hope that this will enable other companies and academic institutions to benefit from this knowledge and consider joining us in our collaborative knowledge sharing.

Author affiliations

  1. Joanne Bowes is at AstraZeneca R&D, Alderley Park, Cheshire SK10 4TG, UK.
  2. Andrew J. Brown is at GlaxoSmithKline, Stevenage, Hertfordshire SG1 2NY, UK.
  3. Jacques Hamon is at the Novartis Institutes for BioMedical Research, Basel CH-4002, Switzerland.
  4. Wolfgang Jarolimek was previously at GlaxoSmithKline, Medicines Research Centre, 37135 Verona, Italy. Present address: Pharmaxis, Drug Discovery, Frenchs Forest 2086, New South Wales, Australia.
  5. Arun Sridhar is at GlaxoSmithKline, Ware, Hertfordshire SG12 0DP, UK.
  6. Gareth Waldron is at Neusentis, Granta Park, Pfizer, Cambridge CB21 6GS, UK.
  7. Steven Whitebread is at the Novartis Institutes for BioMedical Research, Cambridge, Massachusetts 02139, USA.
  8. All authors contributed equally to this work.

Correspondence to: Joanne Bowes1,8 Email: Joanne.Bowes@astrazeneca.com

Correspondence to: Andrew J. Brown2,8 Email: Andrew.j.Brown@gsk.com

Correspondence to: Jacques Hamon3,8 Email: Jacques.Hamon@novartis.com

Correspondence to: Wolfgang Jarolimek4,8 Email: Wolfgang.Jarolimek@pharmaxis.com.au

Correspondence to: Arun Sridhar5,8 Email: Arun.x.Sridhar@gsk.com

Correspondence to: Gareth Waldron6,8 Email: Gareth.Waldron@pfizer.com

Correspondence to: Steven Whitebread7,8 Email: Steven.Whitebread@novartis.com

Published online 30 November 2012

Additional data