Table 1.

GKA potencies in mouse, rat and human

				AZD1656						GKA71
Compound	Human				Rat				Human	Mouse
Dose (mg·kg−1·day−1)a	0.6	–	2.3	–	3	–	10	–	–	2.5	5
	1656	Metb	1656	Met	1656	Met	1656	Met
GKA EC50 (μM)c	0.09	0.04	0.09	0.04	0.1	0.05	0.1	0.05	0.1	0.4	0.4
fud	0.056	0.136	0.056	0.136	0.041	0.041	0.041	0.041	0.013	0.0021	0.0021
Cmax (μM)	1.1	0.12	5	0.47	3.5	0.87	6.9	2.6	–	33.7	53.1
Css,av (μM)e	0.3	0.1	1.7	0.2	0.3	0.2	1.6	0.7	–	26.2	47.1
Cmax,free (μM)	0.062	0.016	0.28	0.064	0.14	0.036	0.28	0.11	–	0.071	0.11
Css,av,free (μM)	0.019	0.008	0.096	0.031	0.013	0.006	0.066	0.027	–	0.055	0.099
Cmax,free/EC50	0.68	0.41	3.1	1.6	1.4	0.71	2.8	2.1	–	0.18	0.28
Css,av,free/EC50	0.21	0.21	1.1	0.76	0.13	0.13	0.66	0.54	–	0.14	0.25
Total Cmax,free/EC50f	1.1		4.7		2.1		5.0		–	0.18	0.28

^aHuman dose based on 70 kg individual (Morrow et al., 2012), oral twice daily. Rat dose oral once daily. Mouse dosed with compound in diet.

^bMet = active metabolite AZD5658; (Morrow et al., 2012).

^cEquipotent against hepatic and pancreatic forms of GK.

^df_u = fraction unbound.

^eC_ss,av = mean drug concentration over 24 h at steady state.

^fCombined AZD1656 + active metabolite activity.