Table 4.

Effect of indacaterol on pharmacodynamic parameters that define GRE-dependent transcription derived by operational model fitting

GR agonist	pKA −Indacaterol	pKA +Indacaterol	τ −Indacaterol	τ +Indacaterol	Ema −Indacaterol	Ema +Indacaterol	n −Indacaterol	n S +Indacaterol
Fluticasone furoate	8.77 ± 0.44	8.71 ± 0.22	1.00 ± 0.05	1.73 ± 0.34	32.2 ± 7.9	67.9 ± 14.9	5.20 ± 4.00	2.29 ± 0.46
Dexamethasone	8.13 ± 0.23	7.58 ± 0.18	0.93 ± 0.35	1.49 ± 0.64	34.6 ± 9.8	83.1 ± 24.6	2.09 ± 0.61	1.53 ± 0.21
GSK 9027b	6.76	6.77	1.55	1.80	16.5	43.9	1.43	1.43
Des-ciclesonideb	8.30	8.14	1.19	1.32	16.3	43.9	1.59	1.45
GW 870086Xb	7.77	7.72	0.72	0.62	16.4	43.8	1.54	1.45

Operational parameters were derived from the data shown in Figures 5 and Supporting Information Fig. S4. Indacaterol was used at a concentration of 100 nM.

^aE_m values for GSK 9027, DC and GW were derived by the comparative method using FF as a reference agonist and, by definition, are equivalent to the E_max values determined directly from the FF E/[A] curve by logistic curve fitting. Accordingly, values of τ assume that FF generates a response that is equivalent to the E_m. However, GR inactivation studies (Figure 5) indicate that this assumption is incorrect. Thus, in the comparative method, E_m and τ values are significantly underestimated and overestimated, respectively, and are italicized for that reason.

^bValues determined from mean data.