Table 3 The substrate specificity, related neurological diseases and clinical trials of small molecular inhibitors

Hydroxamate

Vorinostat (SAHA)

Class I, II

Alzheimer’s disease (Phase I, NCT03056495), Parkinson’s disease, Huntington’s disease, Spinal muscular atrophy, Frontotemporal dementia

[179, 237,238,239,240,241]

Hydroxamate

Panobinostat (LBH589)

Class I, II, IV

Huntington’s disease, Spinal muscular atrophy

[243,244,245]

Hydroxamate

Trichostatin A (TSA)

Class I, IIb

Amyotrophic lateral sclerosis, Spinal muscular atrophy, Parkinson’s disease

[246,247,248,249]

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, 252,253,254,255,256,257, 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)

[262,263,264,265,266,267]

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

[288,289,290,291,292]

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

[313,314,315,316]