. Author manuscript; available in PMC: 2021 Nov 15.

Published in final edited form as: Bioorg Med Chem. 2020 Sep 1;28(22):115734. doi: 10.1016/j.bmc.2020.115734

Table 3.

In vitro ADMET properties of pyrazole 22d.


IC₅₀ (nM)	60
Kin. sol. pH 7.4 (μM)^a	4.5
clogP	3.28
hLM (%)^b	36
rLM (%)^b	71
mLM (%)^b	64
CYP450 IC₅₀ (μM)^c
3A4	3.7
1A2	>100
2C9	9.0
2C19	5.9
2D6	>100
hERG IC₅₀ (μM)^d	8.6
% PPB^e	99.6

Kinetic solubility measured at pH 7.4 by UV/Vis absorbance in PBS buffer (μM).

% Remaining after 30 minutes upon incubation with human (hLM), rat (rLM) and mouse (mLM) liver microsomes (1 mg/mL), at 1 μM test compound concentration.

Five recombinant CYP isoforms were tested for inhibition by the test compound using fluorescence-based assays.

Patch-Xpress patch-clamp assay; compounds were tested (n = 3) in a five-point concentration-response on HEK-293 cells stably expressing the hERG channel.

% PPB = plasma protein binding.