Table 1.

Inhibitory activity against HDAC1‐3 and 6, and physicochemical properties of capless HDACi 6 a–i.

	R1	Physicochemical Properties		IC50 [nM]
		LogD7.4	Solubility[a,e] [μg/mL]	HDAC1[b,e]	HDAC2[b,e]	HDAC3[b,e]	HDAC6[c,e]
CI‐994	‐H	0.84	200±1.80	636.3±114.3	696.3±10.5	262.6±30.7	>10,000[d]
6 a		2.63	1.49±0.14	4.50±0.1	51.4±4.9	3,960±58.5	>10,000[d]
6 b		3.41	0.45±0.04	4.40±0.1	44.7±6.9	1,998±33.0	>10,000[d]
6 c		2.80	0.74±0.01	4.50±0.002	31.6±0.3	1,424±40.5	>10,000[d]
6 d		1.75	16.5±0.30	13.2±1.0	77.2±9.2	8,908±624.0	>10,000[d]
6 e		1.70	37.7±3.61	76.7 ± 9.2	100.5±5.4	635.8±49.5	>10,000[d]
6 f		1.77	42.0±0.19	207.3±4.4	333.3±5.1	17,350±2,420	>10,000[d]
6 g		1.97	7.66±0.08	93.5±2.4	118.3±4.0	767.5±31.7	>10,000[d]
6 h		1.79	1.58±0.14	153.2±22.1	227.6±7.8	2,873±523.0	>10,000[d]
6 i		2.20	3.72±0.44	329.4±20.8	211.3 ±5.4	5,867±23.2	>10,000[d]
vorinostat	–	0.99	255±3.71	113.0±16.9	191.4±15.4	109.5±9.7	21.7±3.2

[a] PBS buffer, pH=7.4; [b] preincubation of enzyme and inhibitor 1 h at 25 °C; [c] preincubation of enzyme and inhibitor 15 min at 25 °C; [d] <25 % inhibition at stated concentration, [e] mean ±SD, at least two independent experiments.