Beyond the human genome: examples of nuclear receptor analysis in model organisms and potential for drug discovery.
The nuclear receptor (NR) superfamily is a large group of related, pharmacologically important receptors, comprising the targets for over 10% of commonly prescribed drugs. Cross-genome analysis of NR sequence, structure, and biological function, provides an important source of information on the function of human NRs and thus plays a role in NR drug discovery. For example, research on the pregnane X receptor (PXR; NR1I2), constitutive androstane receptor (CAR; NR1I3), hepatocyte nuclear factor 4 (HNF4; NR2A1), and farnesoid X receptor (FXR) illustrate how the study of nonhuman orthologs has provided new insights into NR biology and has increased our understanding of human NRs and orphan NR function. Understanding differences between humans and pharmacological model species may provide useful tools for the development of new NR-binding drugs.
Nuclear Receptor Discovery Research, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA.
Jodi M
JM
Maglich
Ann E
AE
Sluder
Tim M
TM
Willson
John T
JT
Moore
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000090702:Constitutive Androstane Receptor; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods*
D000090702:Constitutive Androstane Receptor; C000716327:NR1I3 protein, human; D018160:Receptors, Cytoplasmic and Nuclear