Nuclear Receptor Profiling

These SHED descriptors were recently used to profile in silico a chemical library of 2033 molecules against 25 nuclear receptors [31]. As described above, this annotated 

In summary, examples have been provided in which both ligand-based and target-based methods performed decently when profiling compounds against the family of nuclear receptors. Therefore, it is reasonable to say that these methodologies have reached a sufficient level of maturity to be applied sensibly for designing the next generation of chemical libraries directed to entire protein families. 

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Mestres, J., Couce-Martin, L., Gregori-Puigjane, F Cases, M. and Boyer, S. (2006) Ligand-based approach to in silico pharmacology nuclear receptor profiling. 

Mestres J, Martin-Couce L, Gregori-Puigjane E, et al. Ligand-based approach to in silico pharmacology Nuclear receptor profiling. J Chem Inf Model 2006 46 2725-2736. 

Cases M, Garcia-Serna R, Hettne K, Weeber M, van der Lei J, Boyer S, Mestres J. Chemical and biological profiling of an annotated compound library directed to the nuclear receptor family. Curr Top Med Chem 2005 5 763-72. 

Rosenfeld, J.M., Vargas, R., Jr, Xie, W. and Evans, R.M. (2003) Genetic profiling defines the xenobiotic gene network controlled by the nuclear receptor pregnane X receptor. Molecular Endocrinology, 17, 1268-1282. 

Pearce KH, larmone MA, Simmons CA, et al. Discovery of novel nuclear receptor modulating ligands an integral role for peptide interaction profiling. Drug Discov Today 2004 9 741-51. 

Chemical genomics profiling of environmental chemical modulation of hmnan nuclear receptors. Environ Health Perspect 119 1142-1148... 

Nishimura M, Naito S, Yokoi T. Tissue-specific mRNA expression profiles of human nuclear receptor subfamilies. Drug Metab Pharmacokinet 2004 19 135-149. 

Natural variations in nuclear receptors reinforce the idea that nuclear receptors are good candidates for the creation of orthogonal ligand-receptor pairs. For example, the human retinoic acid receptor (RAR) has three subtypes RARa, RAR/ and RARy. These three subtypes differ at 87 amino acids but have only three divergent residues in the binding pocket [11] (Tab. 8.1). However, these three divergent residues are responsible for different binding profiles of synthetic retinoids... 

Gronemeyer H, Laudet V. Transcription factors 3 nuclear receptors. Protein Profile 1995 2 1173-308. 

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