Table 4 The classes of HDACis in clinic
From: The application of histone deacetylases inhibitors in glioblastoma
target | chemical classes | compounds | source | Isotype selectivity | study phase | reference |
|---|---|---|---|---|---|---|
Pan-HDAC | Hydroxamic acid | Vorinostat (SAHA) | Synthetic | class I, II and IV | FDA approval (CTCL) | [121] |
Belinostat(PXD-101) | Synthetic | class I and II | FDA approval (PTCL) | [15] | ||
Panobinostat (LBH-589) | Synthetic | class I, II and IV | FDA approval (PTCL and multiple myelomas) | [122] | ||
Trichostatin A (TSA) | Natural | class I and II | Phase I (Relapsed or Refractory hematologic malignancies ) | NCT03838926 | ||
Quisinostat (JNJ-16241199) | Synthetic | class I and II | phase II (CTCL) | NCT01486277 | ||
WW437 | Synthetic | HDAC 2 and 4 | pre-clinical | [123] | ||
short chain fatty acids | Pivaloyloxmethyl butyrate (AN-9) | Synthetic | class I and IIa | phase II (melanoma) phase I (CLL) | NCT00087477 NCT00083473 | |
Sodium Butyrate (NaB) | Natural | class I and IIa | phase I (Colorectal cancer ) | [124] | ||
Sodium Phenylbutyrate (4-PB) | Synthetic | class I and IIa | FDA approval (urea cycle disorders) | [10] | ||
Valproate (valproic acid) | Synthetic | class I and IIa | phase I (Brain and Central Nervous System Tumors) | [125] | ||
Benzamides | Entinostat (MS-275) | Synthetic | class I | phase II (Hodgkin's Lymphoma) | [126] | |
Tacedinaline (CI-994) | Synthetic | class I | phase II (Myeloma) | NCT00005624 | ||
Mocetinostat (MG-0103) | Synthetic | class I and IV | phase I (Hodgkin's Lymphoma) | [127] | ||
Cyclic peptides | Romidepsin (depsipeptide, FK228) | Natural | class I | FDA approval (CTCL) | [128] | |
electrophilic ketones | trapoxins(TPX) | Natural | class I | NA | [129] | |
a-ketoamides | Synthetic | NA | NA | [130] | ||
heterocyclic ketones | Synthetic | NA | NA | [131] | ||
miscellaneous compounds | Diallyl Trisulfide (DATS) | Natural | NA | pre-clinical (glioblastoma) | [132] | |
sirtuin inhibitors | cambinol | Synthetic | SIRT1 and 2 | pre-clinical | [133] | |
EX-527 | Synthetic | SIRT1 and 2 | pre-clinical | |||
sirtinol | Synthetic | SIRT1 and 2 | pre-clinical | |||
nicotinamide | Synthetic | class III | phase III (laryngeal cancer) | |||
specific HDAC | Hydroxamate Derivatives | Azelaic Bishydroxamic Acid (ABHA) | Synthetic | HDAC 3 | NA | [134] |
CBHA (m-carboxycinnamic acid bis-hydroxamide) | Synthetic | HDAC 3 | pre-clinical | [135] | ||
NA | I-7ab | Synthetic | HDAC 3 | NA | [136] | |
RGFP966 | Synthetic | HDAC 3 | pre-clinical (CTCL) | [137] | ||
PCI34051 | Synthetic | HDAC 8 | pre-clinical (T-cell lymphomas or leukemias) | [138] | ||
C149 | Synthetic | HDAC 8 | pre-clinical (T-cell lymphoma and neuroblastoma) | [139] | ||
Benzamides | Ricolinosta(ACY-1215) | Synthetic | HDAC 6 | phase II (relapsed/refractory lymphoid malignancies ) | NCT02091063 | |
tubacin | Synthetic | HDAC 6 | pre-clinical (ALL) | [140] | ||
Polyketides | Depudecin | Natural | HDAC 1 | NA | [71] | |
sirtuin inhibitors | SEN196 | Synthetic | SIRT1 | NA | [141] | |
COMPOUND 6J | Synthetic | SIRT2 | NA | [142] | ||
JGB1741 | Synthetic | SIRT1 | NA | [143] | ||
bromodomain | BET inhibitors | JQ1 | Synthetic | BRD4 | pre-clinical (CAA) | [144] |
I-BET | Synthetic | BET | pre-clinica (Breast and lung cancer) | [145] | ||
BY27 | Synthetic | BD2 | NA | [146] | ||
hybrid molecules | chimeric | CUDC907 | Synthetic | HDAC /PI3K | phase II (Thyroid Cancer) | NCT03002623 |
CUDC101 | Synthetic | EGFR/Her-2/HDAC 1 | Phase I (head and neck, gastric, breast, liver, and non-small cell lung cancer) | NCT01171924 |