TABLE 5.

pkCSM predictions for compounds 21, 41, and Tofacitinib.

ADMET			41	21	43	46	Tofacitinib
Absorption	Water solubility	(Log mol/L)	−2.999	−2.892	−2.953	−4.029	−3.526
	Caco-2 permeability	(Log Papp, 10−6 cm/s)	0.534	1.23	0.633	0.796	1.36
	Intestinal absorption (human)		69.134	89.671	72.856	79.729	93.481
Distribution	VDss (human)	(Log L/kg)	1.141	0.011	0.268	0.013	0.402
	Fraction unbound (human)	(Fu)	0.339	0.381	0.058	0	0.41
	BBB permeability	(Log BBB)	−1.482	−0.029	−1.291	−1.282	−0.752
	CNS permeability	(Log PS)	−4.556	−1.429	−3.311	−3.549	−0.752
Metabolism	CY21D6	Substrate	No	No	No	No	No
	CYP3A4		No	No	Yes	Yes	No
	CY41A2	Inhibitor	Yes	Yes	No	No	Yes
	CY21C19		No	No	No	Yes	No
	CY21C9		No	No	No	Yes	No
	CY21D6		No	No	No	No	No
	CYP3A4		No	No	Yes	Yes	No
Excretion	Total Clearance	(Log mL/min/kg)	0.105	−16.253	0.466	0.262	0.848
	Renal OCT2 substrate	(Yes/No)	No	No	No	No	No
	AMES		No	No	No	No	No
Toxicity	Skin Sensitization		No	No	No	No	No
	Hepatotoxicity		Yes	No	Yes	Yes	Yes