Table 1 Inhibition of HDAC isozymes and tumour cell proliferation (IC50, nM)

From: R306465 is a novel potent inhibitor of class I histone deacetylases with broad-spectrum antitumoral activity against solid and haematological malignancies

   

Liver extract

 

Enzyme substrate

HDAC1-IP Ac-H4

HDAC8

MAL unselective

B61 HDAC1

B12 HDAC6

A2780 proliferation

R306465

3.31±0.78

23±17

886±85

51±8

1541±290

39±17

Vorinostat

73±26

370±314

132±7

1032±201

150±9

1157±578

Panobinostat

0.23±0.06

283±29

75±4

47±5

89±12

4.6±1.8

MS-275

>1000

>10 000

Inactive

Inactive

Inactive

376±169

TSA

1.67±0.22

135±51

12±1.2

13.3±1.4

20.7±2.6

23±8

  1. Abbreviations: HDAC=histone deacetylase; TSA=trichostatin A
  2. Inhibition of HDAC activity with R306465 (JNJ-16241199), panobinostat, vorinostat and MS-275 was assessed using a number of different assays: for HDAC1 activity assays, HDAC1 was immunoprecipitated from A2780 cell lysates as indicated in the Methods section and incubated with a concentration range of the indicated HDAC inhibitor. Recombinant HDAC8 activity was measured as indicated in the Methods section. Finally, HDAC isotype activity was measured in rat liver extract using an HDAC1-selective (B61), -unselective (MAL) and an HDAC6-selective (B12) substrate (Heltweg et al, 2004). A2780 tumour cell proliferation was measured using a standard MTT colorimetric assay as indicated in the Methods section. Results are expressed as average IC50 values (nM)±s.d. for three independent experiments.
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