Target selection in drug discovery

Speaker Profile

Muralidhara Padigaru is the Senior Principal Scientist at the Dept of Pharmacology, Nicholas Piramal Research Centre. He holds a doctorate degree in Parasite Immunology, PGIMER, Chandigarh, India and masters degree in Medical Microbiology, Mangalore University, India. He has done bachelors in chemistry, botany and zoology, from the Mangalore University, India.

His research experience include:

• June 2004 to date: Senior Principal Scientist, Dept. of Pharmacology, Nicholas Piramal Research Centre
• December 1999 to May 2004: Senior Research Scientist, Drug Discovery, CuraGen Corporation,
• October 1998 to Dec 1999: Postdoctoral Fellow, Dept. of Molecular Genetics, Albert Einstein College of Medicine, NY.
• Sept 1997 to Sept 1998: Postdoctoral Fellow, Unit on Gene Mapping and Expression, Clinical Neurogenetics Branch, National Institute of Mental Health, Bethesda, MD.
• Aug 1995 to Aug 1997: Manager, DNA Sequencing Facility, BioServe Biotechnologies Ltd, MD.
• June 1993 to June 1995: Postdoctoral Fellow, AstraZeneca Research Centre, Bangalore, India
• Marh 1989 to Marh 1993: Graduate Student, Dept of Parasitology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
• Aug 1988 to Feb 1989: Tutor, JSS Medical School, Mysore, India. Taught medical microbiology to medical undergraduates.

Synopsis

Human genome project and the remarkable progress in molecular biology have led to the identification of numerous proteins that determine the biology of normal and disease conditions. This has opened up immense opportunities for formation of hypotheses regarding functional modulation of defined proteins that are linked to diseases and could be potentially used to identify new drugs. Such disease-linked proteins are commonly referred to as targets.

The basis of such hypotheses can range from an attractive scientific theory to information obtained from genetic analysis of tissues from patients with a particular disease, and the process of confirming such hypotheses is broadly termed ’target validation’.

Target identification and validation in commercial organisations may range from two or three targets as in a start-up company, to 30-50 targets in a multinational pharmaceutical company. This involves investment of private finance with the long-term purpose of providing a realistic financial return within an acceptable timeframe. Clearly, research target selection takes place in an environment that is strongly influenced by financial considerations; there is an interactive relationship between investors, potential consumers and the corporate.

Targets are selected from chosen therapeutic areas approved by the company board with the aim of marketing a potential ‘blockbuster drug’, which is much used by stock analysts to indicate annual sales of the drugs in access of US $1 billion. Apart from the ‘blockbuster drug’, there are ‘me-too’ targets, which have no hypothesis at the inception of the research but address a medical improvement over an existing drug and aim to discover a patentable new chemical entity (NCE) that would enhance the intellectual property portfolio for the company.