Table 2.
Overview of the main HDAC inhibitors and the combinations tested.
| HDACi Classes | HDAC Inhibitor | Target HDAC Class | Preclinical Combinations | Clinical Trials Combinations |
|---|---|---|---|---|
| Hydroximates | Trichostatin A | pan * | Chaetocin [64] Decitabine + DZNep [65] |
|
| Vorinostat (SAHA) | pan * | ATRA [66,67,68] MK-0457 [69] NPI-0052 [70] Cytarabine [71] Etoposide [71] GX15-070 [72] AZD1775 [73] BPR1J-340 [74] BMN673 [75] |
Decitabine [76,77] Idarubicin [78] Idarubicin + Cytarabine [79] Alvocidib [80] GO + AZA [81,82] Sorafenib + Bortezomib [83] |
|
| Panobinostat (LBH589) | pan * | Decitabine [84,85] AZA [86] ABT-199 [87] MK-1775 [88] BC2059 [89] SP2509 [90] JQ1 [91] AC220 [92] Bortezomib [93] CXCR4 antagonist [94] Doxorubicin [95] DZNep [96] |
AZA [97] GSK2879552 [98] Cytarabine + Idarubicin [99] Daunorubicin + Cytarabine [100] Cytarabine + Mitoxantrane [101] |
|
| Belinostat (PXD101) | pan * | ATRA [102,103] DZNep + ATRA [104,105] DZNep + ATRA + Idarubicin [104,105] Bortezomib [106] Pevenedistat [107] |
||
| Givinostat (ITF2357) | pan * | |||
| Resminostat (4SC201) | pan | |||
| Abexinostat (PCI-24781) | pan | |||
| Quisinostat (JNJ-26481585) | pan | |||
| Pracinostat (SB939) | pan | SB1518 [108] | AZA [109,110,111] | |
| Tefinostat (CHR-2845) | pan | |||
| CHR-3996 | I | |||
| Benzamides | Entinostat | I | AZD6244 [112] RAD001 [113] Decitabine [114] |
AZA [115,116] |
| Mocetinostat | I, IV | |||
| Cyclic peptides | Romidepsin | I | ATRA [117] Decitabine [118] AZA [119] |
|
| Apicidin | I | |||
| Trapoxin A | I, II | ATRA [120] | ||
| Aliphatic acids | Valproic acid | I, IIa | ATRA [121,122] Decitabine [123,124,125] GO [126] AZA [127] Retinoid IIF [128] NPI-0052 [129] PR-171 [129] Curcumin [130] Hydroxiurea [131] 6-mercaptopurine [131] Dasatinib [132] Bortezomib [133,134] Cytarabine [135] Nutlin-3 [136] |
ATRA [137,138,139,140,141] Cytarabine [142,143] Hydroxiurea [131] 6-mercaptopurine [131] Decitabine [123,124,125] AZA [127] |
| Butyric acid | I, II | |||
| Phenylbutyric acid | I, II |
* According to Bradner et al. [144] these HDACi do not demonstrate a preference for Class IIa enzymes at pharmacologically relevant concentrations, suggesting that the target HDAC classes for these HDACi are HDAC I, II, III, and VI. GO: Gemtuzumab ozogamicin; AZA: Azacitidine; ATRA: retinoic acid.