Table 2.

Calculated ADMET (Absorption, Distribution, Metabolism, Elimination and Toxicity) properties of PM-C, 1, 2, and 5a-d.

Heading	PM-C	1	2	5a	5b	5c	5d	Range 95% of Drugs
cLogPo/w	4.476	4.889	5.637	2.496	3.200	3.132	3.746	−2.0/6.5
cLogS	−5.031	−6.250	−6.331	−4.126	−4.744	−4.945	−5.419	−6.5/0.5
cLogKhsa	0.364	0.568	0.628	0.108	0.209	0.240	0.319	−1.5/1.5
cLogBB	0.219	0.376	1.039	−1.138	−0.681	−0.890	−0.444	−3.0/1.2
CNS Activity	+	+	++	− −	+/−	−	+/−	− − (inactive) ++ (active)
cLogHERG	−4.511	−4.436	−4.259	−4.586	−4.583	−4.627	−4.515	concern below −5
cPCaco	1298	1338	7162	131	277	175	344	<25 poor >500 great
clogKp	−2.518	−2.594	−1.215	−4.245	−3.667	−4.111	−3.617	Kp in cm/hr
Percent Human Oral Absorption ±20%	100	100	100	79	89	85	94	<25% poor
Jorgensen Rule	0	1	1	0	0	0	0	maximum 3
Lipinski Rule	0	1	2	0	0	0	0	maximum 4
# Stars (violation of the 95% range)	2	2	2	0	1	1	1	0-5

cLogPo/w: predicted octanol/water partition coefficient. cLogS: predicted aqueous solubility, log S. S in mol dm⁻³ is the concentration of the solute in a saturated solution that is in equilibrium with the crystalline solid. cLogKhsa: prediction of binding to human serum albumin. cLogBB: predicted brain/blood partition coefficient. Note: Predictions are for orally delivered drugs. CNS Activity: predicted central nervous system activity on a−2 (inactive) to +2 (active) scale. cLogHERG: predicted IC₅₀ value for blockage of HERG K⁺ channels. cPCaco: Predicted apparent Caco-2 cell permeability in nm/sec; Caco-2 cells are a model for the gut-blood barrier. Predictions are for non-active transport. cLogKp: predicted skin permeability, log K. Percent Human-Oral Absorption ±20%: predicted human oral absorption on 0 to 100% scale; the prediction is based on a quantitative multiple linear regression model; the assessment uses a knowledge-based set of rules, including number of metabolites, number of rotatable bonds, logP, solubility, and cell permeability. Jorgensen Rule or Rule of Three: number of violations of Jorgensen’s rule of three. The three rules are: cLogS > −5.7, cPCaco > 22 nm/s, # Primary Metabolites < 7. Compounds with fewer (and preferably no) violations of these rules are more likely to be orally available. Lipinski Rule or Rule of Five: number of violations of Lipinski’s rule of five. The four rules are: mol_MW < 500, cLogPo/w < 5, HB donor ≤ 5, HB acceptor ≤ 10. Compounds that satisfy these rules are considered drug-like. # Stars (violation of the 95% range): number of property or descriptor values that are outside the 95% range of similar values for known drugs. A large number of stars suggests that a molecule is less drug-like than molecules with few stars.