H. Martin Seidel, Ph.D.
Institute Director
Though Nuclear Receptors (NRs) form a relatively small gene family of 48 members, a remarkable percentage are the targets of drugs currently on the market. More than a third of the 48 members (17 in all) are targets of currently marketed therapeutics, and 20 of the 200-most-prescribed drugs target NRs.
NRs are particularly attractive drug targets because many have evolved to bind small, hydrophobic ("drug-like") molecules, and intra-family selectivity is well-precedented. In addition, because they serve as both receptors and transcription factors with a high degree of conformational plasticity, NRs offer validated, mechanistic avenues for obtaining tissue- or gene-selective action. Furthermore, some NRs are orphan receptors without any known ligands and therefore represent novel opportunities for both research and drug discovery. In order to be able to exploit this attractive target family, GNF has developed considerable NR-related drug discovery capabilities, including relevant NR expertise, reagents, and tools.
Selected Publications
- Epple R, Russo R, Azimioara M, Cow C, Xie Y, Wang X, Wityak J, Karanewsky D, Gerken A, Iskandar M, et al. 3,4,5-Trisubstituted isoxazoles as novel PPARdelta agonists: Part 1. Bioorg Med Chem Lett 2006;16(16):4376-80.
- Laffitte BA, Chao LC, Li J, Walczak R, Hummasti S, Joseph SB, Castrillo A, Wilpitz DC, Mangelsdorf DJ, Collins JL, et al. Activation of liver X receptor improves glucose tolerance through coordinate regulation of glucose metabolism in liver and adipose tissue. Proc Natl Acad Sci U S A 2003;100(9):5419-24.
