Table 4 Microsome stability assessment and CYP inhibition profile of selected HDACis.

From: 1,3-Diphenylureido hydroxamate as a promising scaffold for generation of potent antimalarial histone deacetylase inhibitors

Compound

CYP450% inhibition

@ 10 µM

Half-life−T = t1/2

(in minutes)a

Intrinsic clearance—Clint (µL/min/mg)

1A2

2C9

2D6

3A4

Human

Mouse

Human

Mouse

6c

32

18

*b

*

39.6

4.4

17.0

158

7c

22

*

*

*

 > 120

4.1

 < 6.0

169

8a

48

*

*

*

 > 120

10.1

 < 6.0

69.0

8b

42

*

*

*

66.0

4.0

10.0

173

8c

*

*

*

*

98.8

2.5

7.0

281

8d

*

*

*

*

 > 120

13.8

 < 6.0

50.0

Furafyllinec

81

*

*

*

n.a.

n.a.

n.a.

n.a.

Sulfaphenazole

*

94

*

*

n.a.

n.a.

n.a.

n.a.

Quinidine

*

*

89

*

n.a.

n.a.

n.a.

n.a.

Ketoconazoled

*

*

*

97

n.a.

n.a.

n.a.

n.a.

Sunitinib

n.a.e

n.a.

n.a.

n.a.

22.3

9.1

31.0

76.0

  1. aHalf-life (t1/2) in 1 mg/mL hepatic microsomes.
  2. bInhibition < 10%.
  3. cTested concentration: 40 µM.
  4. dTested concentration: 1.0 µM.
  5. en.a.: not applicable.
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