The application of BacMam technology in nuclear receptor drug discovery.
The nuclear receptor (NR) superfamily represents a major class of drug targets for the pharmaceutical industry. Strategies for the development of novel, more selective and safer compounds aimed at these receptors are now emerging. Reporter assays have been used routinely for the identification and characterisation of NR ligands. As the NR drug development process evolves, the increase in screening demand in terms of both capacity and complexity has necessitated the development of novel assay formats with increased throughput and flexibility. BacMam technology, a modified baculovirus system for over-expressing genes of interest in mammalian cells has helped answer this requirement. BacMam has many advantages over traditional gene delivery systems including high transduction efficiencies, broad cell host range, speed, cost and ease of generation and use. As outlined in this review, the technology has shown itself to be robust and efficient in various NR assay formats including transactivation (ER alpha/beta, MR, PR and PXR) and transrepression (GR-NFkappaB). In addition, the flexibility of this system will allow greater multiplexing of receptor, reporter, and cell host combinations as NR assays become more complex in order to relate better to relevant cellular and biological systems.
Boudjelal
Mohamed
M
Department of Gene Expression and Protein Biochemistry, Discovery Research Biology, GlaxoSmithKline Discovery Research, Harlow, UK.
Mason
Sarah J
SJ
Katso
Roy M
RM
Fleming
Jonathan M
JM
Parham
Janet H
JH
Condreay
J Patrick
JP
Merrihew
Raymond V
RV
Cairns
William J
WJ
D000818:Animals; D016367:Baculoviridae / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics*; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000235:genetics; D013678:Technology, Pharmaceutical / Q000379:methods*; D014162:Transfection / Q000379:methods*
D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid