Table 3.
The substrate specificity, related neurological diseases and clinical trials of small molecular inhibitors
| HDACi | ||||
|---|---|---|---|---|
| Class | Compound | HDAC specificity | Related neurological diseases and clinical trials | References |
| Hydroxamate | Vorinostat (SAHA) | Class I, II | Alzheimer’s disease (Phase I, NCT03056495), Parkinson’s disease, Huntington’s disease, Spinal muscular atrophy, Frontotemporal dementia | [179, 237–241] |
| Hydroxamate | Panobinostat (LBH589) | Class I, II, IV | Huntington’s disease, Spinal muscular atrophy | [243–245] |
| Hydroxamate | Trichostatin A (TSA) | Class I, IIb | Amyotrophic lateral sclerosis, Spinal muscular atrophy, Parkinson’s disease | [246–249] |
| Fatty acid | Sodium butyrate (NaBu) | Class I, II | Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Spinal muscular atrophy, Polyglutamine diseases (e.g., SCA3, SBMA) | [179, 185, 252–257, 261] |
| Fatty acid | Valproic acid (VPA) | Class I, II | Alzheimer’s disease (Phase I, NCT01729598, Phase II, NCT00088387, Phase III, NCT00071721), Huntington’s disease (Phase II, NCT00095355), Parkinson’s disease, Amyotrophic lateral sclerosis (NCT00136110; Phase II, NCT03204500) | [262–267] |
| Fatty acid | Sodium Phenylbutyrate (4-PBA) | Class I, II | Alzheimer’s disease (Phase II, NCT03533257), Huntington’s disease (Phase II, NCT00212316), Parkinson’s disease (Phase I, NCT02046434), | [167, 268, 270, 271] |
| Fatty acid | AMX0035 | Class I, II | Amyotrophic lateral sclerosis (Phase II, NCT03127514, Phase III, NCT05021536); Alzheimer’s disease (Phase III, NCT03533257) | [272] |
| Benzamide | Entinostat (MS-275) | Class I | Alzheimer’s disease | [273] |
| Benzamide | RGFP966 | HDAC3 | Huntington’s disease, Alzheimer’s disease | [172, 274] |
| Benzamide | RGFP109 | HDAC1/3 | Huntington’s disease, Parkinson’s disease | [193, 275] |
| Benzamide | M344 | class I and IIb | Spinal muscular atrophy, Alzheimer’s disease | [276, 277] |
| Benzamide | K560 | HDAC1, HDAC2 | Parkinson’s disease | [278] |
| Benzamide | Nicotinamide (NAM) | Class III | Friedreich's ataxia (Phase II, NCT01589809), Parkinson Disease (NCT03568968, Phase II, NCT04044131), Alzheimer’s disease (Phase II, NCT03061474, Phase II, NCT04044131) | [279] |
| Benzamide | HDACi 4b and 136 | HDAC1, HDAC3 | Huntington’s disease | [280, 281] |
| Cyclic tetrapeptide | Romidepsin (FK228) | HDAC1, HDAC2 | Alzheimer’s disease | [170, 282] |
| Miscellaneous | mercaptoacetamide-based compound W2 | Class II | Alzheimer’s disease | [283] |
| Miscellaneous | CM-144 | HDACs, DMNT1, G9a and PDE5 | Alzheimer’s disease | [284] |
| Miscellaneous | CKD-510 | HDAC6 | Charcot-Marie-Tooth disease (Phase I, NCT04746287) | NA |
| Miscellaneous | CKD-504 | HDAC6 | Huntington’s disease (Phase I, NCT03713892), Alzheimer’s disease | [285] |
| Miscellaneous | Resveratrol (RVT) | HDAC, DNMT and LSD1 inhibitor | Alzheimer’s disease, Amyotrophic lateral sclerosis (Phase II, NCT04654689), Spinal muscular atrophy | [288–292] |
| HAT activator | ||||
| Compound | HAT specificity | Related neurological diseases and clinical trials | ||
| CTPB | p300 | Parkinson’s disease | [309] | |
| HMTi | ||||
| Compound | HMT specificity | Related neurological diseases and clinical trials | ||
| BIX-01294 | G9a | Alzheimer’s disease | [177, 302, 304] | |
| UNC0642 | G9a/GLP | Alzheimer’s disease | [177, 303, 304] | |
| HDMi | ||||
| Compound | HDMT specificity | Related neurological diseases and clinical trials | ||
| Vafidemastat (ORY-2001) | LSD1 | Alzheimer’s disease (Phase II, NCT03867253) | [306] | |
| GSK-J4 | KDM6A/B, KDM5B/C | Parkinson’s disease | [307] | |
| BRD domain inhibitor | ||||
| Compound | BRD specificity | Related neurological diseases and clinical trials | ||
| JQ1 | BRD2, BRD3, BRD4, BRDT | Alzheimer’s disease, Parkinson’s disease, levodopa-induced dyskinesia, Amyotrophic lateral sclerosis | [313–316] | |