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. Author manuscript; available in PMC: 2020 Aug 21.
Published in final edited form as: ACS Chem Neurosci. 2019 Aug 5;10(8):3769–3777. doi: 10.1021/acschemneuro.9b00281

Table 1. Summary of the potency and mechanism of HDAC inhibitors, and of their effect on human PGRN and H3K9ac levels at 1 μM concentration.

Color shadings relate to kinetic mechanisms (cyan: fast- on/fast-off, orange: mechanism A, red: mechanism B of slow-binding kinetics).

Compound Mechanism of binding and potency (Ki(,1): nM, dis. t½: min)
 Effect on PGRN
(1 μM, NPCs)		 Effect on H3K9ac
(1 μM, NPCs)
HDAC1 HDAC2 HDAC3*
1 (SAHA) Ki = 1.3 (± 0.05)30 Ki = 1.6 (± 0.05)30 Ki = 5.0 (± 0.2)30 >2 fold incr.‡, 10 >20 fold incr.‡, 10
2 (SATK) Ki = 9800 (± 6700)26
Dis. t½ = 41 (± 17)		 Ki = 11000 (± 4000)26
Dis. t½ = 87 (± 22)		 Ki, 1 = 570 (± 260)26
Ki ~1126
Dis. t½ ≥ 139		 No change No change
3 (tacedinaline) Ki, 1 = 1450 (± 320)
Ki ~1
Dis. t½ ≥ 1386		 Ki, 1 = 2190 (± 510)
Ki ~14
Dis. t½ ≥ 139		 Ki, 1 = 3560 (± 400)
Ki = 105 (± 86)
Dis. t½ ≥ 50		 Decrease‡ ~18 fold incr‡
5 (panobinostat) Ki, 1 = 33 (± 26)
Ki ~0.1
Dis. t½ ≥ 41		 Ki, 1 = 4.7 (± 2.5)
Dis. t½ > 105 		Ki, 1 = 15 (± 5)
Ki ~0.1
Dis. t½ ≥ 63		 ~2.3 fold incr. ~36 fold incr.
6 (trapoxin A) Ki ~0.003
Dis. t½ ~6931		 Dis. t½ > 105 Ki, 1 = 0.59 (± 0.29)27
Dis. t½ > 105 		~2.4 fold incr. ~5.0 fold incr.
7a (TpxBAoda) Ki = 6.6 (± 0.5)27 Ki = 3.9 (± 0.4)27 Ki = 0.78 (± 0.05)27 No change ~2.8 fold incr.
7b (TpxBAsu(Et))† Ki = 500 (± 90)27 Ki = 400 (± 20)27 Ki = 500 (± 80)27 No change ~2.1 fold incr.
7c (TpxBAsuha) Ki, 1 = 0.60 (±0.12)27
Dis. t½ > 105 		Ki, 1 = 0.13 (±0.11 )27
Dis. t½ > 105 		Ki, 1 = 1.4 (± 0.4)27
Ki ~0.0227
Dis. t½ ≥ 173		 ~2.2 fold incr. ~6.3 fold incr.
8a (apicidin) Ki = 0.824 (± 0.003) Ki = 0.619 (± 0.004) Ki = 0.051 (± 0.002)27 ~1.7 fold incr. ~3.3 fold incr.
9b (ApiAAsu(Et))† Ki = 10 (± 1)27 Ki = 11 (± 2)27 Ki = 15 (± 3)27 ~1.4 fold incr. ~2.1 fold incr.
9c (ApiAAsuha) Ki, 1 = 0.32 (± 0.06)27
Dis. t½ > 105 		Ki, 1 = 0.35 (±0.10)27
Dis. t½ > 105 		Ki, 1 = 1.8 (± 0.6)27
Ki ~0.0427
Dis. t½ ≥ 77		 ~2.5 fold incr. ~6.4 fold incr.
10 (romidepsin) Ki, 1 = 0.88 (± 0.18)
Ki ~0.02
Dis. t½ ≥ 26		 Ki, 1 = 0.47 (± 0.09)
Ki ~0.009
Dis. t½ ≥ 41		 Ki, 1 = 1.3 (± 0.4)27
Dis. t½ > 105 		~4.1 fold incr. ~2.3 fold incr.
10d (RomiAla, Dha) Ki = 690 (± 3)27 Ki = 370 (± 50)27 Ki = 800 (± 100)27 No change Decrease
*

HDAC3 in combination with the DAD domain of NCoR2.

†

Inhibition data corresponding to the carboxylic acid hydrolyzed species (TpxBAsu and ApiAAsu, respectively)27.

‡

Treatment performed at 10 μM concentration.