Table 1 Summary of epigenetic approaches and molecules
From: Drugging the epigenome in the age of precision medicine
Epigenetic effector class | Drug | Modality | Marketed/developed by | Status/uses |
|---|---|---|---|---|
1st generation DNA methyltransferase inhibitor | 5-Azacytidine (Onureg, Vidaza) | Small molecule | Bristol Myers Squibb | FDA approved for the treatment of myelodysplastic syndrome |
5-Aza-2′-deoxycytidine (decitabine; Inqovi) | Small molecule | Astex/Taiho | FDA approved for the treatment of myelodysplastic syndrome | |
Pseudoisocytidine | Small molecule | Various | Clinical development discontinued for hepatotoxicity concerns | |
5,6-Dihydro-5-azacytidine (DHAC) | Small molecule | Various | Clinical development discontinued for cardiotoxicity concerns | |
2nd generation DNA methyltransferase inhibitor | Guadecitabine (SGI-110) | Small molecule | Astex Pharmaceuticals | Development discontinued due to lack of Phase 3 efficacy |
Fluorocyclopentenylcytosine (RX-3117, TV-1360) | Small molecule | Rexhan Pharmaceuticals (Ocuphire Pharma) | Clinical development paused due to weak Phase 2a data | |
1st generation histone deacetylase inhibitors | Suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) | Small molecule | Merck | FDA approved for the treatment of cutaneous T cell lymphoma |
Romidepsin (Istodax) | Small molecule | Bristol Myers Squibb | FDA approved for the treatment of cutaneous T cell lymphoma; accelerated approval for peripheral T cell lymphoma withdrawn | |
Sodium butyrate/butyric acid | Small molecule | Various | Research compound to explore HDAC inhibition in model systems | |
2nd generation histone deacetylase inhibitors | Belinostat (Beleodaq) | Small molecule | Acrotech Biopharma | FDA approved for peripheral T cell lymphoma |
Panobinostat (Farydak) | Small molecule | Secura Bio | FDA accelerated approval for peripheral T cell lymphoma withdrawn | |
Entinostat | Small molecule | Syndax | Clinical development paused due to lack of Phase 3 efficacy | |
Tucidinostat (Chidamide, Epidaza or Hiyasta) | Small molecule | Chipscreen Biosciences | CFDA approved for peripheral T cell lymphoma; PMDA approved for adult T cell leukemia-lymphoma | |
Histone methyltransferase inhibitors | Pinometostat | Small molecule | Epizyme (Ipsen) | Clinical development discontinued due to lack of efficacy |
Tazemetostat (Tazverik) | Small molecule | Epizyme (Ipsen) | FDA approved for relapsed/refractory follicular lymphoma and epithelioid sarcoma | |
GSK3326595 | Small molecule | GlaxoSmith Kline | Clinical development paused | |
Lysine demethylase inhibitors | Tranylcypromine | Small molecule | Various | FDA approved for depression |
Ladademstat (ORY-1001) | Small molecule | Oryzion Genomics | In clinical development for multiple tumor types | |
GSK2879552 | Small molecule | GlaxoSmith Kline | Clinical development discontinued due to unfavorable risk/benefit to patients | |
Bromodomain inhibitors | Molibresib | Small molecule | GlaxoSmithKline | Clinical development discontinued |
Pelabresib (CPI-06160) | Small molecule | Constellation Pharmaceuticals (MorphoSys) | Clinical development ongoing in myelofibrosis (Phase 3) | |
Apabetalone (RVX-208) | Small molecule | Resverlogix | Clinical development ongoing in cardiovascular, infectious disease (COVID-19), and renal disease (Phase 3) | |
IDH inhibitor | Ivosidenib (Tibsovo) | Small molecule | Servier | FDA approved for the treatment of acute myeloid leukemia and cholangiocarcinoma |
Enasidenib (Idhifa) | Small molecule | Bristol Myers Squibb/Servier | Relapsed/refractory acute myeloid leukemia | |
Precision epigenomic modulators | OTX-2002 | Epigenomic programming | Omega Therapeutics | IND cleared by FDA; clinical trial to begin in 2H2022 |
ST-502 | Zinc finger protein transcription factor | Sangamo Therapeutics | Preclinical development ongoing | |
EPIC-321 | Epigenetic engineering | Epic Bio | Preclinical development ongoing |