Table 5. HDACi Compounds That Induce Apoptosis in B- and T-cell Cancer Cells.
| HDACi | Class | Target of HDACi | Clinical trial stage | Hematopoietic malignancy (Patient and Cell Line) | Combination treatments that induce apoptosis | Refs |
|---|---|---|---|---|---|---|
| Butyrate (NaB) | Short-chain fatty acid | Class 1, 2a | Phase I, II | B-lymphoma, BL | Cisplatin, Etoposide | [142, 185, 186] |
| Valproic Acid (VPA) | Short-chain fatty acid | HDAC1-5, 7, 8, 10 | Phase I, II, III | AML, CML, CLL, DLBCL, HL, MM, NHL, NK cell lymphoma, SLL, T-cell lymphoma | 5-Azacytidine, ATRA, Bortezomib, Cambinol, Cyclophosphamide, Decitabine, Enzastaurin, Etoposide, EX527, Imatinib, Pioglitazone, Prednisone, Rituximab, Sirtinol, Temozolomide, Vincristine | [142, 187-193] |
| Tricostatin A (TSA) | Hydroxamate | Class 1, 2, 4 | AML, B-lymphoma, DLBCL, EBV+ BL, NHL | Decitabine | [142, 146, 186, 194-197] | |
| Vorinostat, Suberoylanilide hydroxamic acid (SAHA) | Hydroxamate | Class 1, 2, 4 | Phase I, II, III | ALL, AML, CLL, CML, CTCL, DLBCL, HL, MCL, MM, NHL | 17-AAG, ABT-737, Azacitidine, Bexarotene, Bortezomib, Carboplatin, Carfilzomib, Cladribine, Cyclophosphamide, Decitadine, Eltrombopag, Enzastaurin, Etoposide, Ifosfamide, Lenalidomide, Melphalan, NPI-0052, Prednisone, Rituximab | [67, 134, 142, 146, 198-209] |
| Belinostat (PDX101) | Hydroxamate | Class 1, 2, 4 | Phase I, II, III | ALL, AML, CLL, MM, MCL, NHL, PTCL, T-cell lymphoma | 17-AAG, Azacitidine, Bortezomib | [142, 188, 206, 210-214] |
| Dacinostat (LAQ824) | Hydroxamate | Class 1, 2, 4 | Phase I | Acute eukemia, AML progenitor cells, CLL, meyloid leukemias | Decitabine | [142, 215-219] |
| Panobinostat (LBH589) | Hydroxamate | Class 1, 2, 4 | Phase I, II, III | AML, CLL, CML, CTCL, DLBCL, HL, MCL, MM, NHL, NK/T-cell lymphoma, PTCL | 17-AAG, Bortezomib, Carboplatin, Cytarabine, Etoposide, Everolimus, Idarubicin, Imatinib, Ifosfamide, Lenalidomide, Pemetrexed, Rituximab | [134, 142, 203, 220-224] |
| Suberic bishydroxamic acid (SBHA) | Hydroxamate | Class 1, 2, 4 | ALL, Leukemia, MM | ABT-737 | [142, 145, 225, 226] | |
| Azelaic bishydroxamic acid (ABHA) | Hydroxamate | Class 1, 2, 4 | EBV+ B-cell lines | ABT-737 | [142, 227] | |
| SK-7041 | Hydroxamate | HDAC1, 2 | Meyloid leukemia | Imatinib | [228, 229] | |
| ITF-A and ITF-B | Hydroxamate | Class 1, 2, 4 | Phase I | DLBCL, MCL, SMZL | [151] | |
| Tubacin | Hydroxamate | Class 2b | ALL, AML, CML, EBV+ BL, MM | 17-AAG, Bortezomib | [142, 230-233] | |
| JNJ 26481585 | Hydroxamate | Class 1, 2, 4 | Phase I | CTCL, Leukemia, MM | Bortezomib, Dexamethasone | [234] |
| PCI-24781 | Hydroxamate | Class 1, 2, 4 | Phase I | HL, NHL | Bortezomib, Pazopanib | [235, 236] |
| Entinostat (MS-275) | Benzamide | HDAC1-3 | Phase I, II | ALL, AML, CML, HL, MM | Azacitadine, Imatinib, Isotretinoin, Sargramostim, Sorafenib, Rapamycin, Rituximab | [142, 237-241] |
| Mocetinostat (MGCD-0103) | Benzamide | HDAC1-3, 10, 11 | Phase I, II | AML, CLL HL, NHL | 5-azacitadine, Bortezomib, Docetaxel, Gemcitabine, GX15-070 | [242-250] |
| Romidepsin (FK228) | Cyclic tetrapeptide | Class 1, 2, 4 | Phase I, II, III | ALL, AML, CLL, CTCL, DLBCL, MM, MCL, NHL, PTCL, SLL | Bortezomib, Carboplatin, Cyclophosphamide, Decitadine, Etoposide, Ifosfamide, Prednisone, Rituximab, Vincrstine | [206, 210, 223, 251-260] |
| Apicidin | Cyclic tetrapeptide | HDAC1, 3 | APL, CML | Imatinib, TRAIL | [142, 261-264] | |
| Nicotinamide | Vitamin B member | Sirtuins | CLL | [265] | ||
| Tenovin-6 (TV-6) | Small Molecule | SIRT1 | CML | Imatinib | [266] | |
| Amurensin G | Natural Product | SIRT1 | TRAIL-resistant leukemia | [267] |
Cell types: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; APL, acute promyelocytic leukemia; BL, Burkitt's lymphoma; CLL, chronic lymphocytic leukemia; CML, chronic myelogenous leukemia; CTCL, cutaneous T-cell lymphoma; DLBCL, diffuse large B-cell lymphoma; EBV+ BL, Epstein-Barr virus-positive BL; HL, Hodgkin's lymphoma; MCL, mantle cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin's lymphoma; PTCL, peripheral T-cell lymphoma; SLL, small lymphocytic lymphoma.
Drug type: 17-AAG (Hsp90 inhibitor); ABT-737 (BH3-mimetic); ATRA (all-trans retinoic acid); azacitidine (DNA methyltransferase inhibitor); bexarotene (antineoplastic agent); bortezomib (proteasome inhibitor); cambinol (sirtuin inhibitor); carboplatin (antineoplastic agent); carfilzomib (proteasome inhibitor); cisplatin (alkylating agent); cladribine (adenosine deaminase inhibitor); cyclophosphamide (alkylating agent); cytarabine (DNA synthesis inhibitor); decitabine (DNA methyltransferase inhibitor); dexamethasone (glucocorticoid steroid); docetaxel (anti-mitotic agent); eltrombopag (thrombopoeitin receptor agonist); enzastaurin (PKCβ inhibitor); etoposide (topoisomerase inhibitor); everolimus (mTOR inhibitor); EX527 (sirtuin inhibitor); gemcitabine (nucleoside analog); GX15-070 (BH3-mimetic); idarubicin (topoisomerase II inhibitor); imatinib (tyrosine kinase inhibitor); ifosfamide (alkylating agent); isotretinoin (retinoic acid analog); lenalidomide (tumor necrosis factor [TNF] inhibitor); melphalan (alkylating agent); NPI-0052 (proteasome inhibitor); pazopanib (tyrosine kinase inhibitor); pemetrexed (folate antimetabolites); pioglitazone (thiazolidinedione); prednisone (glucocorticoid prodrug); rituximab (anti-CD20 antibody); sargramostin (recominant GM-CSF); sirtinol (sirtuin inhibitor); sorafenib (tyrosine kinase inhibitor); temozolomide (alkylating agent); TRAIL (TNF-related apoptosis-inducing ligand ); vincristine (mitotic inhibitor).