ADMET

COMPOUNDS

Type

Properties

58a

58b

58c

58d

58e

58f

58g

58h

58i

58j

Amsc

Etop

Absorption

Water solubility

(log mol/L)

−4.358

−4.426

−4.179

−4.754

−5.034

−5.125

−4.855

−5.203

−4.669

−4.392

−4.889

−3.487

Caco-2 permeability

(log Papp in 10 cm/s)

1.367

1.373

1.335

1.150

1.193

1.253

1.372

1.251

1.371

0.593

0.579

0.403

Intestinal absorption (human) (% Absorbed)

94.024

93.957

94.926

92.892

95.07

91.044

91.946

90.977

92.036

89.82

94.938

75.614

Skin Permeability

(log Kp)

−2.787

−2.786

−2.79

−2.817

−2.832

−2.876

−2.883

−2.874

−2.807

−2.917

−2.734

−2.735

P-glycoprotein substrate

No

No

No

No

No

Yes

Yes

Yes

Yes

Yes

Yes

Yes

P-glycoprotein I inhibitor

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

P-glycoprotein II inhibitor

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Distribution

VDss (human)

(log L/kg)

−0.007

0.012

−0.157

0.032

0.038

0.170

0.012

0.189

0.092

−0.028

−0.987

−0.218

Fraction unbound (human)

0.028

0.025

0.042

0.052

0.061

0.046

0.066

0.043

0.079

0.078

0.120

0.038

BBB permeability

(log BB)

−0.006

−0.007

−0.013

−0.006

−0.423

0.122

0.115

0.120

0.154

−0.164

−0.096

−1.567

CNS permeability

(log PS)

−1.522

−1.499

−1.676

−1.664

−1.871

−1.365

−1.519

−1.343

−1.546

−1.670

−2.200

−4.115

Metabolism

CYP2D6 substrate

No

No

No

No

No

No

No

No

No

No

No

No

CYP3A4 substrate

No

No

No

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

CYP1A2 inhibitor

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

CYP2C19 inhibitor

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

CYP2C9 inhibitor

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

CYP2D6 inhibitor

No

No

No

No

No

No

No

No

No

No

No

No

CYP3A4 inhibitor

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

Yes

No

Excretion

Total Clearance

(log ml/min/kg)

0.116

0.094

−0.042

0.141

0.276

−0.017

−0.035

−0.039

−0.028

−0.004

0.246

−0.068

Renal OCT2 substrate

No

No

No

No

No

No

No

No

No

No

No

No

Toxicity

AMES toxicity

Yes

Yes

Yes

Yes

No

Yes

Yes

Yes

Yes

Yes

Yes

No

Max. tolerated dose (human)

(log mg/kg/day)

0.254

0.254

0.236

−0.008

0.063

−0.011

−0.039

−0.01

0.085

−0.093

0.266

0.171

hERG I inhibitor

No

No

No

No

No

No

No

No

No

No

No

No

hERG II inhibitor

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

Oral Rat Acute Toxicity (LD50) (mol/kg)

2.743

2.752

2.701

2.797

2.812

2.948

2.910

2.955

2.777

2.879

1.960

3.250

Oral Rat Chronic Toxicity (LOAEL)

(log mg/kg_bw/day)

1.118

1.092

1.243

1.585

1.481

1.011

1.163

0.983

1.702

1.258

1.400

2.429

Hepatotoxicity

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

Yes

No

Skin Sensitisation

No

No

No

No

No

No

No

No

No

No

No

No

T. Pyriformis toxicity (log ug/L)

0.393

0.392

0.395

0.424

0.388

0.513

0.563

0.512

0.427

0.479

0.287

0.285

Minnow toxicity

(log mM)

0.207

0.061

0.541

−0.236

−1.443

0.064

0.397

−0.082

0.555

0.722

−0.078

2.217