Table 2. In Vitro ADME and PK Parameters for Lead MEK Inhibitors.

				rat PK parametersa
compd	MDCKb	RLMc	HLMc	Cl (mL/h/kg)	oral t1/2 (h)	F %	AUC/dosed
7	399	80.1	30.8	8324	1.5	19	0.05
8	43	16.2		755	9.1	78	1.57
12	207	31.5	46.3	2101	5.4	101	0.85
13	210	40.5	35.8	5958	4.9	86	0.25
18	99	–4.5	2.6	800	11.4	58	1.03
1	105	22.4	13.8	3565	6.1	77	0.35

^aCompounds were prepared as amorphous solids and dosed at 5 mg/kg in female CD rats.

^bCell permeability P_app nm/s.

^c% Conversion in the presence of rat and human liver microsomes at 0.5 mg/mL microsomal concentration supplemented with NADPH and at 15 μM substrate concentration at 37 °C for 30 min.

^dOral AUC (0–t) normalized to dose (μM h/mg/kg).