Table 2 ADMET prediction of abemaciclib and the hit compounds with good binding against DYRK1A using the AI drug lab (https://ai-druglab.smu.edu/).

From: Identification of novel DYRK1A inhibitors as treatment options for alzheimer’s disease through comprehensive in silico approaches

Molecular property

45,934,388

CNP0344929

CNP0360040

CNP0309850

CNP0426983

46,220,502

(Control drug)

Molecular weight (g/mol)

372.08

396.16

416.15

420.08

328.09

506.27

Number of heteroatoms

8

6

8

8

6

10

Number of rotatable bonds

3

6

6

2

5

7

Number of Rings

3

3

3

4

3

5

Number of HA

7

6

8

8

5

8

Number of HD

4

1

4

5

3

1

Absorption

Caco-2 permeability (log(cm/s))

−5.22

−5.19

−5.14

−5.3

−5.29

−5.03

HIA (%)

72.82

74.6

72.47

70.29

70.67

74.14

Pgp inhibition (%)

50.27

44.42

54.14

56.56

42.44

47.75

log D7.4

2.07

1.87

1.89

2.07

1.68

1.95

Aqueous solubility (log(mol/L))

−4.41

−4.23

−4.44

−4.51

−4.48

−4.36

Oral bioavailability (%)

44.11

47.4

41.9

38.53

45.79

48.2

Distribution

BBB (%)

27.6

19.85

20.86

18.08

33.73

25.63

PPBR (%)

45.79

50.38

47.89

46.68

57.19

52

Metabolism

CYP2C9 inhibition (%)

59.04

64.31

61.11

54.46

45.03

67.68

CYP2D6 inhibition (%)

88.97

96.08

93.11

89.74

96.87

100.37

CYP3A4 inhibition (%)

41.14

36.03

37.11

36.62

33.7

30.54

CYP2C9 substrate (%)

35.71

34.74

39.56

37.41

42.16

41.22

CYP2D6 substrate (%)

52.82

55.35

51.24

59.21

57.85

52.09

CYP3A4 substrate (%)

39.19

39.17

36.36

35.18

33.97

38.48

Excretion

Half-Life (hr.)

65.4

66.16

68.59

68.55

77.12

139.11

CL-Hepa (uL min−1 (106 cells)−1)

41.19

41.03

46.88

41.97

44.1

31.85

CL-Micro (mL min−1 g−1)

33.78

49.8

48.17

42.31

40.1

45.17

Toxicity

hERG blockers (%)

36.32

38.8

41.76

40.35

37.17

47.98

Ames (%)

40.64

46.78

43.88

45.81

40.71

46.9

DILI (%)

46.09

49.66

46.82

47.58

44.31

52.5

LD50 [-log (mol/kg)]

2.29

2.95

2.58

2.54

1.9

2.75

  1. Aqueous solubility: soluble -2 ̴ 0, slightly soluble -4 ̴ -2, insoluble < -4; BBB- blood-brain barrier: optimal- ≤30%, Medium- 30 – 70%, poor-≥70%; Caco2- Cell effective permeability: > -5.15 is optimal; HIA- human intestinal absorption: Poor- ≤30%, Medium- 30 – 80%, optimal-≥80%; Pgp-inhibition- p-glycoprotein inhibition: optimal- ≤30%, Medium- 30 – 70%, poor-≥70%; PPBR- plasma protein binding rate: optimal- ≤90%, poor-≥90%; hERG blockers- human ether-ether-go-go gene blocker: optimal- ≤30%, Medium- 30 – 70%, poor-≥70%; Ames mutagenicity: optimal- ≤30%, Medium- 30 – 70%, poor-≥70%; and DILI- drug-induced liver injury: optimal- ≤30%, Medium- 30 – 70%, poor-≥70%; CL-Hepa: clearance from the hepatocytes; CL-Micro: clearance from the microsomes.
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