Table 3.

Anticipated ADMET characteristics of the top potent inhibitors.

ADME Parameters	XF7	T3D2489	T3D2672	T3D2378
Absorption
Water solubility	−3.5	−3.0	−3.4	−2.5
Caco2 permeability	0.5	−0.2	−0.1	0.3
Intestinal absorption (human)	93.5	47.6	56.7	95.0
Skin Permeability	−2.7	−2.7	−2.7	−3.2
P-glycoprotein substrate	Yes	Yes	Yes	Yes
P-glycoprotein I inhibitor	Yes	No	Yes	No
P-glycoprotein II inhibitor	Yes	No	Yes	No
Distribution
VDss (human)	0.3	1.6	0.6	1.3
BBB permeability	−1.1	−0.7	−1.7	0.2
CNS permeability	−2.5	−4.1	−3.4	−2.6
Metabolism
CYP2D6 substrate	No	No	No	No
CYP3A4 substrate	Yes	No	Yes	Yes
CYP1A2 inhibitior	No	No	No	No
CYP2C19 inhibitior	Yes	No	No	No
CYP2C9 inhibitior	Yes	No	No	No
CYP2D6 inhibitior	No	No	No	No
CYP3A4 inhibitior	Yes	No	No	No
Excretion
Total Clearance	0.8	1.4	−0.1	0.8
Toxicity
AMES toxicity	No	No	No	No
Max. tolerated dose (human)	0.4	0.3	−0.3	−0.4
hERG I inhibitor	No	No	No	No
hERG II inhibitor	Yes	Yes	No	Yes
Oral Rat Acute Toxicity (LD50)	3.3	2.7	2.8	2.4
Oral Rat Chronic Toxicity (LOAEL)	1.1	3.1	2.7	0.7
Hepatotoxicity	Yes	Yes	Yes	Yes
Skin Sensitisation	No	No	No	No
T. Pyriformis toxicity	0.3	0.3	0.3	0.6
Minnow toxicity	2.4	2.2	0.9	4.7