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Physicochemical Property

Property	Predicted values	Suggestions	Meaning & Preference	Reference
LogS (Solubility)	log mol/L ( μg/mL)	> 10 μg/ml	Optimal: higher than -4 log mol/L <10 μg/mL: Low solubility; 10–60 μg/mL: Moderate solubility; >60 μg/mL: High solubility	Book: ISBN: 9787562832287. pp. 14 J PHARMACOL TOX MET. 2000, 44 (1), 235−249;
LogD7.4 (Distribution Coefficient D)		1~5	< 1: Solubility high; Permeability low by passive transcellular diffusion; Permeability possible via paracellular if MW < 200; Metabolism low. 1 to 3: Solubility moderate; Permeability moderate; Metabolism low. 3 to 5: Solubility low; Permeability high; Metabolism moderate to high. > 5: Solubility low; Permeability high; Metabolism high.	Methods and principles in medicinal chemistry 18 (pp. 21–45). Weinheim: Wiley-VCH.
LogP (Distribution Coefficient P)		0~3	Optimal: 0< LogP <3 LogP <0: poor lipid bilayer permeability. LogP >3: poor aqueous solubility.	Book: ISBN: 3-906390-22-5. pp. 127–182.

Absorption

Property	Predicted values	Probability	Suggestions	Meaning & Preference	Reference
Papp (Caco-2 Permeability)	cm/s		> -5.15 cm/s	Optimal: higher than -5.15 Log unit or -4.70 or -4.80	J CHEM INF MODEL. 2016, 56 (4), pp 763–773.
Pgp-inhibitor	---			The Pgp-inhibitor & non-inhibitor classification criteria refers the reference.	J CHEM INF MODEL. 2010. 50(6): p. 1034-1041. J MED CHEM. 2011. 54(6): p. 1740-1751.
Pgp-substrate	---			More likely to be a Pgp substrate: N+O ≥ 8; MW > 400; Acid with pKa > 4 More likely to be a Pgp non-substrate: N+O ≤ 4; MW < 400; Acid with pKa < 8	J DRUG TARGET. 11, 391–406.
HIA (Human Intestinal Absorption)	---			≥30%: HIA+; <30%: HIA-	RSC ADV. 2017, 7, 19007-19018
F (20% Bioavailability)	---			≥20%: F20+; <20%: F20-	MOL PHARMACEUT, 2011. 8(3): p. 841-851 J PHARMACEUT BIOMED, 2008. 47(4): p. 677-682.
F (30% Bioavailability)	---			≥30%: F30+; <30%: F30-	MOL PHARMACEUT, 2011. 8(3): p. 841-851 J PHARMACEUT BIOMED, 2008. 47(4): p. 677-682.

Distribution

Property	Predicted values	Probability	Suggestions	Meaning & Preference	Reference
PPB (Plasma Protein Binding)	%		90%	Significant with drugs that are highly protein-bound and have a low therapeutic index.	ISBN: 978-0-1236-9520-8. pp. 194
VD (Volume Distribution)	L/kg		0.04~20 L/kg	Optimal: 0.04-20L/kg; Range: <0.07L/kg: Confined to blood, Bound to plasma protein or highly hydrophilic; 0.07-0.7L/kg: Evenly distributed; >0.7L/kg: Bound to tissue components (e.g., protein, lipid),highly lipophilic.	Book: ISBN: 9787562832287. pp. 174 Book: ISBN: 978-0-1236-9520-8. pp. 229
BBB (Blood–Brain Barrier)	---			BB ratio >=0.1: BBB+; BB ratio <0.1: BBB- These features tend to improve BBB permeation: H-bonds (total) < 8–10; MW < 400–500; No acids.	J NEUROCHEM. 70, 1781–1792

Metabolism

Property	Predicted values	Probability	Meaning & Preference	Reference
P450 CYP1A2 inhibitor	---		Molecules that labeled inhibitor in PubChem BioAssay were regarded as inhibitor.	NAT BIOTECHNOL. 2009, 27(11): 1050-1055. BIOINFORMATICS. 2013, 29(16): 2051-2052.
P450 CYP1A2 Substrate	---		Molecules that labeled substrate in PubChem BioAssay were regarded as substrate. Characteristics of CYP1A2 substrate: 0.08< LogP <3.61; Planar amines and amides	NAT BIOTECHNOL. 2009, 27(11): 1050-1055. BIOINFORMATICS. 2013, 29(16): 2051-2052.
P450 CYP3A4 inhibitor	---		Molecules that labeled inhibitor in PubChem BioAssay were regarded as inhibitor. Strategies to Reduce CYP3A4 Inhibition: Decrease the lipophilicity (LogD 7.4); Add steric hindrance to the heterocycle para to the nitrogen; Add an electronic substitution (e.g., halogen) that reduces the pKa of the nitrogen.	NAT BIOTECHNOL. 2009, 27(11): 1050-1055. BIOINFORMATICS. 2013, 29(16): 2051-2052.
P450 CYP3A4 substrate	---		Molecules that labeled substrate in PubChem BioAssay were regarded as substrate. Characteristics of CYP3A4 substrate: 0.97< LogP <7.54; Large molecules	NAT BIOTECHNOL. 2009, 27(11): 1050-1055. BIOINFORMATICS. 2013, 29(16): 2051-2052. ISBN: 978-0-1236-9520-8. pp. 162
P450 CYP2C9 inhibitor	---		Molecules that labeled inhibitor in PubChem BioAssay were regarded as inhibitor.	NAT BIOTECHNOL. 2009, 27(11): 1050-1055. BIOINFORMATICS. 2013, 29(16): 2051-2052.
P450 CYP2C9 substrate	---		Molecules that labeled substrate in PubChem BioAssay were regarded as substrate. Characteristics of CYP2C9 substrate: 0.89< LogP <5.18; Acidic (Nonionized)	MOL INFORM. 2011. 30(10): p. 885-895. J CHEM INF MODEL. 2013. 53(12): p. 3373-3383. ISBN: 978-0-1236-9520-8. pp. 162
P450 CYP2C19 inhibitor	---		Molecules that labeled inhibitor in PubChem BioAssay were regarded as inhibitor.	NAT BIOTECHNOL. 2009, 27(11): 1050-1055. BIOINFORMATICS. 2013, 29(16): 2051-2052.
P450 CYP2C19 substrate	---		Molecules that labeled substrate in PubChem BioAssay were regarded as substrate.	NAT BIOTECHNOL. 2009, 27(11): 1050-1055. BIOINFORMATICS. 2013, 29(16): 2051-2052.
P450 CYP2D6 inhibitor	---		Molecules that labeled inhibitor in PubChem BioAssay were regarded as inhibitor.	MOL INFORM. 2011. 30(10): p. 885-895. J CHEM INF MODEL. 2013. 53(12): p. 3373-3383.
P450 CYP2D6 substrate	---		Molecules that labeled substrate in PubChem BioAssay were regarded as substrate. Characteristics of CYP2D6 substrate: 0.75< LogP <5.04; Basic (Ionized)	MOL INFORM. 2011. 30(10): p. 885-895. J CHEM INF MODEL. 2013. 53(12): p. 3373-3383. ISBN: 978-0-1236-9520-8. pp. 162

Elimination

Property	Predicted values	Suggestions	Meaning & Preference	Reference
T 1/2 (Half Life Time)	h	> 0.5 h	Range: >8h: high; 3h< Cl < 8h: moderate; <3h: low	ISBN: 978-0-1236-9520-8. pp. 236
CL (Clearance Rate)	mL/min/kg		Range: >15 mL/min/kg: high; 5mL/min/kg< Cl < 15mL/min/kg: moderate; <5 mL/min/kg: low	ISBN: 978-0-1236-9520-8. pp. 236

Toxicity

Property	Predicted values	Probability	Suggestions	Meaning & Preference	Reference
hERG (hERG Blockers)	---			Where molecules with IC50 < 40 μM were regarded as blockers. Features may lead to hERG blocker: A basic amine (positively ionizable, pKa >7.3). Hydrophobic/lipophilic substructure(s) (ClogP >3.7). Absence of negatively ionizable groups or oxygen H-bond acceptors.	TRENDS PHARMACOL SCI. 2005, 26(3): 119-124 ISBN: 978-0-1236-9520-8. pp. 213 MOL PHARM. 2016, 13(8):2855–2866
H-HT (Human Hepatotoxicity)	---			The H-HT positive(+) & negative(-) classification criteria refers the reference.	CHEM RES TOXICOL, 2016, 29(5): 757-767.
AMES (Ames Mutagenicity)	---			Ames positive(+) & negative(-): significantly induces revertant colony growth at least in one out of usually five strains, otherwise, negative.	J CHEM INF MODEL. 2012, 52(11): 2840-2847.
SkinSen (Skin sensitization)	---			Sensitizer & Non-sensitizer: The (r)LLNA experimental value. (r)LLNA: (Reduced) local lymph node assay.	TOXICOL APPL PHARM, 2015 , 284 (2) :262-272
LD50 (LD50 of acute toxicity)	-log mol/kg ( mg/kg)		> 500 mg/kg	Median lethal dose (LD50) usually represents the acute toxicity of chemicals.It is the dose amount of a tested molecule to kill 50 % of the treated animals within a given period. High-toxicity: 1~50 mg/kg; Toxicity: 51~500 mg/kg; low-toxicity: 501~5000 mg/kg.	CHEM RES TOXICOL, 2009, 22 (12), pp 1913–1921 J CHEMINFORMATICS, 2016 , 8 (1) :6
DILI (Drug Induced Liver Injury)	---			The DILI positive(+) & negative(-) classification criteria refers the reference.	J CHEM INF MODEL, 2015, 55(10) :2085-2093
FDAMDD (Maximum Recommended Daily Dose)	---			The FDAMDD positive(+) & negative(-) classification criteria refers the reference.	CHEMOMETR INTELL LAB, 2015, 146:494-502

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   Computational Biology & Drug Design Group, School of Pharmaceutical Sciences, Central South University.