TABLE 2

Cellular binding and Kp_uu values obtained using two independent methods

f_u,cyto was derived from Kp_sat (saturation method), whereas f_u,cell,hom was measured in ZR75-1 homogenate using rapid equilibrium dialysis (binding method). Physicochemical data (logD_pH7.5) were calculated by ADMET Predictor. Data are expressed as means ± S.E.

Compound	logD_pH7.5	f_u,med	Saturation Method		Binding Method
Compound	logD_pH7.5	f_u,med	f_u,cyto	Kp_uu,cyto^{^a}	f_u,cell,hom	Kp_uu,cell,hom^{^a}
WM-8014	2.9	0.180 ± 0.006	0.0057 ± 0.0001	0.069 ± 0.007	0.025 ± 0.003	0.30 ± 0.06
WM-1119	1.9	0.69 ± 0.03	0.43 ± 0.03	0.68 ± 0.11	0.16 ± 0.03	0.26 ± 0.08
Compound 1	4.5	0.040 ± 0.005	0.00115 ± 0.00006	0.16 ± 0.05	0.00015 ± 0.00007	0.02 ± 0.01
Compound 2	2.8	0.0114 ± 0.0006	0.00036 ± 0.00002	0.08 ± 0.02	0.0064 ± 0.0004	1.4 ± 0.3
Compound 3	3.1	0.00299 ± 0.00008	0.0000911 ± 0.0000006	0.044 ± 0.004	0.0005 ± 0.0002	0.25 ± 0.12
Compound 4	2.3	0.26 ± 0.01	0.05 ± 0.01	0.26 ± 0.12	0.051 ± 0.006	0.25 ± 0.10
Compound 5	2.7	0.16 ± 0.01	0.0145 ± 0.0004	0.19 ± 0.03	0.0110 ± 0.0009	0.14 ± 0.03
Compound 6	2.4	0.37 ± 0.03	0.09 ± 0.01	0.38 ± 0.13	0.053 ± 0.007	0.22 ± 0.08
Compound 7	1.9	0.130 ± 0.003	0.077 ± 0.004	0.33 ± 0.06	0.076 ± 0.004	0.32 ± 0.06
Compound 8	2.6	0.05 ± 0.01	0.00592 ± 0.00004	0.11 ± 0.02	0.0017 ± 0.0004	0.03 ± 0.01
Compound 9	2.9	0.130 ± 0.005	0.025 ± 0.002	0.22 ± 0.08	0.005 ± 0.002	0.05 ± 0.03
Compound 10	2.1	0.375 ± 0.003	0.29 ± 0.01	0.38 ± 0.03	0.03 ± 0.01	0.05 ± 0.02

↵^a For the calculation of Kp_uu values, the Kp in the fully unsaturated state (Kp_unsat) was used for both methods (eqs. 10 and 14).