. Author manuscript; available in PMC: 2016 Jun 10.

Published in final edited form as: J Med Chem. 2015 Aug 4;58(15):5863–5888. doi: 10.1021/acs.jmedchem.5b00423

Table 5.

In Vitro ADMET Profile for 33

	hepatic CL_int (µL/mL/min)^b						% PPB^d		MDCK-MDR1 permeability P_app (×10⁻⁶ cm/s)

solubility^a	H	R	M	cyno	CYP inhibition (IC₅₀) 2C9, 2C19, 2D6, 3A4	hERG^c (IC₅₀)	H	R	A-B	B-A	class
>100 µM	<0.7	<0.7	<0.7	0.7	All >34 µM	>30 µM	99.9	99.4	74.7	82.2	high permeability

Kinetic solubility measured in PBS (pH 7.4).

Hepatic intrinsic clearance; H = human; R = rat; M = mouse; cyno = cynomolgus monkey.

Patch-Xpress’ patch-clamp assay; compounds were tested (n = 3) in a five-point concentration–response on HE293 cells stably expressing the hERG channel.

% PPB = plasma protein binding.