Table 3 Pharmacokinetic of PVL prediction

Lipinski rule of 5

Molecular Weight

 < 500

480.378

302.238

463.371

286.239

318.237

448.38

290.271

154.121

1701.206*

416.382

502.78

Numeric (g/mol)

Acceptor Hydrogen

 < 10

13*

7

12*

6

8

11*

6

3

46*

9

8

Numeric (AH)

Donor Hydrogen

 < 5

9*

5

7

4

6

7

5

3

25*

5

6

Numeric (DH)

LogP

 < 5

− 0.8333

1.988

− 1.1709

2.2824

318.237*

− 0.2445

1.5461

0.796

4.8381

0.3443

0.68

Numeric (MLogP)

Absorption

Water solubility

 < 0,4 mol/L (low)

− 2.904*

− 2.925*

− 2.848*

− 3.04*

− 2.915*

− 2.863*

− 3.117*

− 2.069*

− 2.892*

− 2.784*

− 2.841

Numeric (mol/L)

0,4–41 mol/L (Medium)

 > 41 mol/L (high)

Caco2 permeability

 > 0.90

− 1.34*

− 0.229*

0.336*

0.032*

0.095*

0.306*

− 0.283*

0.49*

− 3.581*

0.24*

0.801

Numeric (Papp in 10⁻⁶ cm/s)

Intestinal absorption (human)

Low: 0–20%

33.394

77.207

42.972

74.29

65.93

48.052

68.829

71.174

0*

59.319

50.545

Numeric (% Absorbed)

Medium: 20–70%

High: 70–100%

Skin Permeability

Likely skin permeable: > -2.5

− 2.735

− 2.735

− 2.735

− 2.735

− 2.735

− 2.735

− 2.735

− 2.727

− 2.735

− 2.736

− 2.735

Numeric (log K_p)

P-glycoprotein substrate

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No*

Yes

Yes

Yes

Categorical (Yes/No)

P-glycoprotein I inhibitor

No

No

No

No

No

No

No

No

No

No

No

No

Categorical (Yes/No)

P-glycoprotein II inhibitor

No

No

No

No

No

No

No

No

No

Yes*

No

No

Categorical (Yes/No)

Distribution

VDss (human)

Low: < -0.15

1.542

1.559

1.423

1.274

1.317

1.444

1.027

− 1.298*

0.011

− 0.166*

1.2

Numeric (log L/kg)

High > 2.81

Fraction unbound (human)

–

0.265

0.206

0.215

0.178

0.238

0.218

0.235

0.648

0.381

0.199

0.571

Numeric (Fu)

BBB permeability

Low: < 0.1

− 2.078*

− 1.098*

− 1.491*

− 0.939*

− 1.493*

− 1.514*

− 1.054*

− 0.683*

− 8.62*

− 1.232*

− 0.425

Numeric (log BB)

Medium: 0.1–0.2

High: > 0.2

CNS permeability

 > -2 (penetrate BBB)

− 4.747

− 3.065

− 4.068

− 2.228

− 3.709

− 3.908

− 3.298

− 3.305

− 8.582

− 3.584

− 2.871

Numeric (log PS)

 < -3 (Can’t penetrate BBB)

Metabolism

CYP2D6 substrate

No

No

No

No

No

No

No

No

No

No

No

No

Categorical (Yes/No)

CYP3A4 substrate

No

No

No

No

No

No

No

No

No

No

No

Yes

Categorical (Yes/No)

CYP1A2 inhibitor

No

No

Yes*

No

Yes*

Yes*

No

No

No

No

No

No

Categorical (Yes/No)

CYP2C19 inhibitor

No

No

No

No

No

No

No

No

No

No

No

No

Categorical (Yes/No)

CYP2C9 inhibitor

No

No

No

No

No

No

No

No

No

No

No

No

Categorical (Yes/No)

CYP2D6 inhibitor

No

No

No

No

No

No

No

No

No

No

No

No

Categorical (Yes/No)

CYP3A4 inhibitor

No

No

No

No

No

No

No

No

No

Yes*

No

No

Categorical (Yes/No)

Excretion

Total Clearance

− 0.002

0.413*

0.407*

0.215*

0.477*

0.422*

0.462*

0.183*

0.551*

0.477*

0.104*

0.194

Numeric (ml/min/kg)

Renal OCT2 substrate

No

No

No

No

No

No

No

No

No

Yes*

No

No

Categorical (Yes/No)

Toxicity

AMES toxicity

No

No

No

No

No

No

No

No

No

No

No

No

Categorical (Yes/No)

hERG I inhibitor

No

No

No

No

No

No

No

No

No

No

No

No

Categorical (Yes/No)

hERG II inhibitor

No

Yes*

No

Yes*

No

No

No

No

No

Yes*

Yes*

Yes

Categorical (Yes/No)

Hepatotoxicity

No

No

No

No

No

No

No

No

No

No

No

No

Categorical (Yes/No)

Skin Sensitization

No

No

No

No

No

No

No

No

No

No

No

No

Categorical (Yes/No)

T. Pyriformis toxicity

Non-toxic: > 0.5

0.285*

0.288*

0.285*

0.312*

0.286*

0.285*

0.347*

0.273*

0.285*

0.285*

0.241

Numeric (log μg/L)

Toxic: < 0.5