A comparison of GS-5759, a bifunctional β2-adrenoceptor agonist and PDE4 inhibitor, and indacaterol and GSK 256066 in combination on gene expression changes in the BEAS-2B human airway epithelial cell line

GS-5759 is a bifunctional ligand composed of a quinolinone-containing pharmacophore found in several β2-adrenoceptor agonists linked covalently to a phosphodiesterase 4 inhibitor (PDE4) related to GSK 256066 by a pent-1-yn-1-ylbenzene spacer. The object of the study was to detemine if gene expression changes induced by GS-5759 were replicated by a β2-adrenoceptor agonist (indacaterol; Ind) and a PDE4 inhibitor (GSK 256066; GSK) in combination. Microarray analysis was performed on RNA from BEAS-2B cells treated with GS-5759 and a combination of indacaterol and GSK 256066 to identify differentialy expressed genes. Confluent BEAS-2B cells were treated with vehicle, Ind/GSK or GS-5759 for 1h, 2h, 6h or 18h. Total RNA was extracted, quantified (NanoDrop 2000) and the quality of each sample determined by using the Agilent 2100 Lab-on-a-Chip system before being processed for gene expression chnages by Expression Analysis Inc (Dunham, NC, USA).