Table 4.

ADMET profiling of top-5 drug candidates.

ADMET	Property/ Parameter	MP-001-739-296	MP-005-944-636	MP-005-945-924	MP-035-706-028	MP-039-052-338	N3	α-ketoamide
Absorption	Water solubility (log mol/L)	−3.52	−4.74	−2.00	−3.39	−3.29	−3.85	−3.84
	Caco2 permeability (log Papp, 10-6 cm/s)	0.66	0.54	0.50	−0.19	−0.35	0.56	0.38
	Intestinal absorption (% Absorbed)	49.15	85.64	46.12	58.25	68.87	53.99	65.54
	Skin Permeability (log Kp)	−2.73	−2.87	−2.89	−2.74	−2.74	−2.74	−2.75
	P-glycoprotein sub	No	Yes	No	Yes	Yes	Yes	Yes
	P-glycoprotein I inh	No	Yes	No	No	No	Yes	Yes
	P-glycoprotein II inh	No	Yes	No	No	Yes	No	Yes
Distribution	VD (human) (log L/kg)	−0.84	0.19	−0.21	−0.22	0.56	−0.49	0.09
	Fraction unbound (human) (Fu)	0.20	0.22	0.50	0.17	0.09	0.19	0.05
	BBB permeability (log BB)	−0.54	−1.07	−0.99	−1.29	−1.18	−1.41	−1.07
	CNS permeability (log PS)	−2.98	−2.84	−3.57	−3.72	−3.19	−3.97	−3.52
Metabolism	CYP2D6 sub	No	No	No	No	No	No	No
	CYP3A4 sub	Yes	Yes	No	Yes	Yes	Yes	Yes
	CYP1A2 inh	No	No	No	No	Yes	No	No
	CYP2C19 inh	No	Yes	No	No	No	No	No
	CYP2C9 inh	No	No	No	No	Yes	No	No
	CYP2D6 inh	No	No	No	No	No	No	No
	CYP3A4 inh	No	Yes	No	No	Yes	Yes	Yes
Excretion	Total Clearance (log ml/min/kg)	1.24	1.32	0.20	0.12	0.47	0.44	0.16
	Renal OCT2 sub	No	No	No	No	No	No	No
Organ Toxicity to human	Hepatotoxicity#	0.81	0.8	0.84	0.88	0.73	0.64	0.66
	Carcinogenicity#	0.5	0.72	0.85	0.8	0.66	0.52	0.6
	Mutagenicity#	0.85	0.9	0.77	0.72	0.51	0.59	0.63
	Cytotoxicity#	0.61	0.78	0.78	0.79	0.86	0.69	0.51
	AMES toxicity	No	No	Yes	No	No	No	No
	hERG I inhibitor	No	No	No	No	No	No	No
	hERG II inhibitor	No	No	No	No	Yes	Yes	Yes
	Oral Rat AT (LD50) (mol/kg)	2.08	2.23	1.97	2.54	2.53	3.538	2.155
	Oral Rat CT (LOAEL) (log mg/kg_bw/day)	0.68	1.994	3.489	3.154	2.418	3.417	2.142
	Skin Sensitization	No	Yes	No	No	No	No	No
Tox21-Nuclear receptor signaling pathways	AhR#	0.98	0.89	0.85	0.8	0.83	0.91	0.91
	AR#	0.93	0.98	0.96	0.95	0.92	0.95	0.97
	AR-LBD#	0.94	1	0.97	0.97	0.94	0.97	0.98
	Aromatase#	0.85	0.97	0.96	0.81	0.74	0.95	0.91
	ER-Alpha#	0.85	0.58	0.82	0.71	0.6	0.88	0.87
	ER- LBD#	0.92	0.59	0.96	0.92	0.84	0.92	0.96
	PPAR-Gamma#	0.98	0.91	0.98	0.9	0.81	0.92	0.96
Tox21-Stress response pathways	nrf2/ARE	0.83	0.78	0.96	0.86	0.8	0.93	0.93
	HSE	0.83	0.78	0.96	0.86	0.8	0.93	0.93
	MMP	0.67	0.51	0.92	0.7	0.64	0.88	0.69
	p53	0.91	0.82	0.9	0.72	0.69	0.88	0.83
	ATAD5	0.99	0.97	0.96	0.93	0.88	0.95	0.91
Toxicity target*	Receptor#	AR (75.1%)	NF	PG/H S1 (94.3%)	GR (81.9%)	AR (72.3%)	N/A	N/A
Predicted Toxicity	LD50# mg/kg	3000	2000	4000	1500	3919	4000	675
Toxicity Class	Class#	4	4	5	4	5	5	4
Toxicity to environment	T. Pyriformis (log ug/L)	0.39	1.10	0.29	0.29	0.36	0.285	0.291
	Minnow toxicity (log mM)	1.04	−0.49	3.80	3.20	3.57	5.647	2.122
Strong Active		Strong Inactive		Weak Active		Weak Inactive