Chemical approaches to nuclear receptors in metabolism

Abstract

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) sponsored a workshop, "Chemical Approaches to Nuclear Receptors and Metabolism," in April 2009 to explore how chemical and molecular biology and physiology can be exploited to further our understanding of nuclear receptor structure, function, and role in disease. Signaling cascades involving nuclear receptors are more complex and interrelated than once thought. Nuclear receptors continue to be attractive targets for drug discovery. The overall goal of this workshop was to identify gaps in our understanding of the complexity of ligand activities and begin to address them by (i) increasing the collaboration of investigators from different disciplines, (ii) developing a better understanding of chemical modulation of nuclear receptor action, and (iii) identifying opportunities and roadblocks in the path of translating basic research to discovery of new therapeutics.

Fig. 1

Pathway for translation of basic research to applications in the clinic. There is substantial investment from public and nonprofit institutions in basic discovery research and from the pharmaceutical industry in exploratory clinical research, but little investment in the translational research that moves potential therapeutic targets from the discovery phase toward clinical application. This is particularly true when it comes to pre-investigational new drug (Pre-IND) development. ADME, absorption distribution metabolism excretion; GMP, good manufactoring practice; GLP, good laboratory practice; and PK, pharmacokinetics.