Table 6.

In silico assessment of pharmacokinetic (PK) properties for reference (REF) inhibitors and identified hits generated by pkCSM.

PK Properties	Natural Compound Hits		Synthetic Compound Hits		Reference Inhibitors		Cut-Off
	Hit1 (STOCK1N-70463)	Hit2 (STOCK1N-48729)	Hit1 (STOCK1S-95244)	Hit2 (STOCK1S-71515)	REF1	REF2
Molecular weight	447.48	474.56	489.58	489.35	500.60	598.51	≤500 Da
LogP	4.57	4.33	5.30	4.53	7.65	6.47	<5
Rotatable Bonds	9	7	7	9	4	8	<10
HBA	6	4	8	5	3	7	≤10
HBD	1	2	2	3	4	4	≤5
Water solubility	−5.585	−5.078	−3.182	−4.998	−2.892	−2.905	<−10 insoluble to <0 highly soluble
Caco-2 permeability	0.585	1.169	1.101	0.564	0.754	−0.526	>0.90
IA (human)	94.26	100	97.45	82.54	100	64.80	>30
Skin permeability	−2.688	−2.802	−2.735	−2.752	−2.735	−2.735	>−2.5
P-gp substrate	Yes	Yes	No	Yes	Yes	No	No
P-gp I inhibitor	Yes	Yes	Yes	Yes	No	No	No
BBB permeability	−0.862	−0.854	−0.633	−1.136	−0.941	−2.352	>0.3 high to <−1 poor
CYP2D6 inhibitor	No	No	No	No	No	No	No
hERG I inhibitor	No	No	No	No	Yes	No	No
Total clearance	0.544	0.152	−0.023	−0.124	0.813	−0.171	<0.3 low to >0.7 high
Renal OCT2 substrate	No	No	No	No	Yes	No	No

Abbreviations—HBA: Hydrogen Bond Acceptor, HBD: Hydrogen Bond Donor, IA: Intestinal Absorption, P-gp: P-glycoprotein, BBB: Blood–Brain Barrier, hERG: human ether-a-go-go-related gene, OCT2: Organic Cation Transporter 2.