Table 1. Calculated Rate Constants (k_n), Inhibition Constants (K_n), and Dissociation Half-Lives (t_1/2) for Compounds 3, 4, and 5^a.

	HDAC1	HDAC2	HDAC3c
Entinostat (3)
k2 (min–1)	0.5 ± 0.1	0.28 ± 0.04	0.6 ± 0.5
k–2 (min–1)	∼7 × 10–9	∼3 × 10–3	∼7 × 10–3
Ki,1 (nM)	590 ± 400	590 ± 340	∼3200
Ki (nM)	–b	∼6	∼39
t1/2 (min)	>105	≥240	≥95
RGFP966 (4)
k2 (min–1)	0.4 ± 0.1	0.38 ± 0.03	0.3 ± 0.1
k–2 (min–1)	∼2 × 10–2	∼7 × 10–3	∼5 × 10–3
Ki,1 (nM)	1300 ± 1000	1700 ± 400	700 ± 700
Ki (nM)	∼57	∼31	∼13
t1/2 (min)	≥36	≥95	≥131
Compound 5
k1 (nM–1·min–1)	(7.8 ± 0.4) × 10–5	(5.1 ± 0.2) × 10–5
k–1 (min–1)	(3 ± 3) × 10–3	(5 ± 2) × 10–3
Ki (nM)	∼40	∼103
t1/2 (min)	∼220	∼130
k2 (min–1)			0.78 ± 0.08
k–2 (min–1)			∼4 × 10–11
Ki,1 (nM)			25 ± 6
Ki (nM)			–b
t1/2 (min)			<105

^aThe data correspond to mechanism B of slow-binding kinetics, except for the inhibition of HDACs 1 and 2 by compound 5, which follows mechanism A.

^bK_i was not determined because the value of k_–2 obtained by data fitting approached zero.

^cThe HDAC3 enzyme preparation contained the DAD of NCoR2.