# Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)

Source: https://onco.cc/technologies/epigenetic-drugs/  
OnCo record `epigenetic-drugs` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Drugs that change how genes are switched on and off without changing the DNA itself.

## Summary

Azacitidine/decitabine (DNMT) in MDS/AML, HDAC inhibitors in T-cell lymphoma, tazemetostat (EZH2; withdrawn worldwide March 2026 over secondary blood cancers), ivosidenib/vorasidenib (IDH), revumenib/ziftomenib (menin), and BET inhibitors (pelabresib in myelofibrosis). Solid tumour activity is limited so far except for IDH and EZH2 in defined subsets; combinations to re-sensitise to immunotherapy or hormone therapy are the hope.

## Fields

- Kind: Technology
- Status: approved
- Last checked: 2026-09-04
- Principle: Inhibit writers, erasers, or readers of DNA and histone marks, or scaffold proteins that tether them.
- Strengths: Differentiation rather than cytotoxicity; Defined genetic subsets respond
- Limitations: Broad effects; modest solid tumour activity

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Epigenetic_therapy
- Wikipedia: https://en.wikipedia.org/wiki/Epigenetic_therapy

## Connected records

- technologies: [Epigenetic editing (durable gene silencing)](https://onco.cc/technologies/epigenetic-editing/), [IDH inhibitors](https://onco.cc/technologies/idh-inhibitors/), [KAT6 inhibitors](https://onco.cc/technologies/kat6-inhibitors/), [LSD1 inhibitors](https://onco.cc/technologies/lsd1-inhibitors/)
- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Chordoma](https://onco.cc/cancers/chordoma/), [Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms](https://onco.cc/cancers/cmml/), [Epithelioid sarcoma](https://onco.cc/cancers/epithelioid-sarcoma/), [Glioma & glioblastoma](https://onco.cc/cancers/glioblastoma/), [IDH1- and IDH2-mutated acute myeloid leukaemia](https://onco.cc/cancers/aml-idh/), [Myelodysplastic syndromes / neoplasms (MDS)](https://onco.cc/cancers/mds/), [NUT carcinoma (midline carcinoma with NUTM1 rearrangement)](https://onco.cc/cancers/nut-carcinoma/), [Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)](https://onco.cc/cancers/peripheral-t-cell-lymphoma/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- fronts: [Epigenetic & Transcriptional Therapy](https://onco.cc/fronts/epigenetics/)
- targets: [BRD4](https://onco.cc/targets/brd4/), [EZH2](https://onco.cc/targets/ezh2/), [IDH1 / IDH2](https://onco.cc/targets/idh/), [Menin](https://onco.cc/targets/menin/), [TET2](https://onco.cc/targets/tet2/)
- companies: [4SC](https://onco.cc/companies/4sc/), [Amphista Therapeutics](https://onco.cc/companies/amphista-therapeutics/), [Foghorn Therapeutics](https://onco.cc/companies/foghorn-therapeutics/), [K36 Therapeutics](https://onco.cc/companies/k36-therapeutics/), [MorphoSys (Novartis)](https://onco.cc/companies/morphosys/), [ORIC Pharmaceuticals](https://onco.cc/companies/oric-pharmaceuticals/), [Prelude Therapeutics](https://onco.cc/companies/prelude-therapeutics/), [Proxygen](https://onco.cc/companies/proxygen/), [Treeline Biosciences](https://onco.cc/companies/treeline-biosciences/)
- drugs: [Arsenic trioxide](https://onco.cc/drugs/arsenic-trioxide/), [Azacitidine](https://onco.cc/drugs/azacitidine/), [Belinostat](https://onco.cc/drugs/belinostat/), [Decitabine](https://onco.cc/drugs/decitabine/), [Decitabine + cedazuridine (oral)](https://onco.cc/drugs/decitabine-cedazuridine/), [Enasidenib](https://onco.cc/drugs/enasidenib/), [Ivosidenib](https://onco.cc/drugs/ivosidenib/), [Mevrometostat](https://onco.cc/drugs/mevrometostat/), [Olutasidenib](https://onco.cc/drugs/olutasidenib/), [Panobinostat](https://onco.cc/drugs/panobinostat/), [Resminostat](https://onco.cc/drugs/resminostat/), [Revumenib](https://onco.cc/drugs/revumenib/), [Romidepsin](https://onco.cc/drugs/romidepsin/), [Tazemetostat](https://onco.cc/drugs/tazemetostat/), [Tretinoin (all-trans retinoic acid, ATRA)](https://onco.cc/drugs/tretinoin-atra/), [Tucidinostat (chidamide)](https://onco.cc/drugs/tucidinostat/), [Vorasidenib](https://onco.cc/drugs/vorasidenib/), [Vorinostat](https://onco.cc/drugs/vorinostat/), [ZEN-3694](https://onco.cc/drugs/zen-3694/), [Ziftomenib](https://onco.cc/drugs/ziftomenib/)
- trials: [A Clinical Trial of TQB3909 Tablets in Combination With Azacitidine for the Treatment of Myeloid Malignancies](https://onco.cc/trials/nct07011186/), [A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination With Venetoclax in AML (AZTOUND Study)](https://onco.cc/trials/nct04256317/), [A Phase 2 Clinical Study of Ziftomenib in Patients With Relapsed or Refractory NPM1-Mutated Acute Myeloid Leukemia](https://onco.cc/trials/nct07623616/), [A Phase 2 Study of MAX-40279 Combined With Venetoclax and Azacitidine in Unfit Newly Diagnosed Acute Myeloid Leukemia](https://onco.cc/trials/nct07743112/), [A Pivotal Study of APG-2575 (Lisaftoclax) Combined With Azacitidine in the Treatment of Acute Myeloid Leukemia](https://onco.cc/trials/nct06389292/), [A Study Comparing Treatment Preference Between Oral Decitabine/Cedazuridine and Azacitidine in Myelodysplastic Syndrome, Low-Blast Acute Myeloid Leukemia, or Chronic Myelomonocytic Leukemia](https://onco.cc/trials/nct05883956/), [A Study of BL-M11D1 in Combination With Cytarabine + Daunorubicin or Venetoclax + Azacitidine in Patients With Acute Myeloid Leukemia](https://onco.cc/trials/nct07255872/), [A Study of CFI-400945 With or Without Azacitidine in Patients With AML, MDS or CMML](https://onco.cc/trials/nct04730258/), [A Study of Cusatuzumab Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Are Not Candidates for Intensive Chemotherapy](https://onco.cc/trials/nct04023526/), [A Study of Gilteritinib, Venetoclax and Azacitidine as a Combined Treatment for People Newly Diagnosed With Acute Myeloid Leukemia](https://onco.cc/trials/nct05520567/), [A Study of Tagraxofusp in Combination With Venetoclax and Azacitidine in Adults With Untreated CD123+ Acute Myeloid Leukemia Who Cannot Undergo Intensive Chemotherapy](https://onco.cc/trials/nct06456463/), [A Study to Assess Adverse Events and Change in Disease Activity When Intravenous (IV) Pivekimab Sunirine is Given in Combination With Oral Venetoclax and IV or Subcutaneous Azacitidine in Adult Participants With Acute Myeloid Leukemia (AML)](https://onco.cc/trials/nct07581002/), [A Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus ](https://onco.cc/trials/nct04224493/), [A Study to Assess the Safety and Efficacy of Two Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) Harboring IDH Mutations Who Are Not Candidates to Receive Intensive Induction Chemotherapy](https://onco.cc/trials/nct02677922/), [A Study to Compare the Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Best Supportive Care as Maintenance Therapy in Japanese Participants With Acute Myeloid Leukemia (AML) in Complete Remission](https://onco.cc/trials/nct05197426/), [A Study to Learn How PF-06821497 (Mevrometostat) Works in Men With Metastatic Castration-resistant Prostate Cancer.](https://onco.cc/trials/nct06629779/), [AGILE](https://onco.cc/trials/agile/), [An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma](https://onco.cc/trials/nct05876754/), [An Open-label Phase 3b Study of Ivosidenib in Combination With Azacitidine in Adult Patients Newly Diagnosed With IDH1m Acute Myeloid Leukemia (AML) Ineligible for Intensive Induction Chemotherapy.](https://onco.cc/trials/nct05907057/), [APL0406](https://onco.cc/trials/apl0406/), [ASCERTAIN-V](https://onco.cc/trials/ascertain-v/), [AUGMENT-101](https://onco.cc/trials/augment-101/), [AZA-001](https://onco.cc/trials/aza-001/), [BMT CTN 1102](https://onco.cc/trials/bmt-ctn-1102/), [Chidamide in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (R/R PTCL)](https://onco.cc/trials/nct05833724/), [ClarIDHy](https://onco.cc/trials/claridhy/), [Clinical Study of Mitoxantrone Hydrochloride Liposome Injection vs. Chidamide in Patients With Relapsed/Refractory PTCL](https://onco.cc/trials/nct04668690/), [Clinical Trial of BP1001 in Combination With With Venetoclax Plus Decitabine in AML](https://onco.cc/trials/nct02781883/), [FCN-338 in Combination With Azacitidine or Chemotherapy in Myeloid Neoplasms](https://onco.cc/trials/nct06858618/), [IMGN632 as Monotherapy or With Venetoclax and/or Azacitidine for Participants With CD123-Positive Acute Myeloid Leukemia](https://onco.cc/trials/nct04086264/), [INDIGO](https://onco.cc/trials/indigo/), [Ivosidenib in Participants With Locally Advanced or Metastatic Conventional Chondrosarcoma Untreated or Previously Treated With 1 Systemic Treatment Regimen](https://onco.cc/trials/nct06127407/), [KOMET-001](https://onco.cc/trials/komet-001/), [MEVPRO-1](https://onco.cc/trials/mevpro-1/), [PBSS1113 in Combination With Azacitidine to Treat Patients With AML/MDS](https://onco.cc/trials/nct07761533/), [QUAZAR AML-001](https://onco.cc/trials/quazar-aml-001/), [Studies to Assess Ziftomenib in Combination With Ven+Aza or 7+3 in Patients With Untreated NPM1-m or KMT2A-r AML](https://onco.cc/trials/nct07007312/), [Study of Lisaftoclax (APG-2575) Single Agent and Combination With Therapy in Patients Relapsed/Refractory AML](https://onco.cc/trials/nct04501120/), [Study of Olutasidenib and Temozolomide in HGG](https://onco.cc/trials/nct06161974/), [Study of Revumenib in Combination With Intensive Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) With a NPM1 Mutation](https://onco.cc/trials/nct07211958/), [Study of SLS009 (Formerly GFH009) a Potent Highly Selective CDK9 Inhibitor in Patients With Hematologic Malignancies and High-Risk Newly Diagnosed AML](https://onco.cc/trials/nct04588922/), [Tazemetostat with doxorubicin as front-line therapy for advanced epithelioid sarcoma (EZH-301 run-in)](https://onco.cc/trials/tazemetostat-doxorubicin-es/), [This Study Will Explore Whether a Combination of the Investigational Drug Mevrometostat (PF-06821497) and Enzalutamide Will Work Better Than Taking En](https://onco.cc/trials/nct07028853/), [To Evaluate Efficacy of Belinostat or Pralatrexate in Combination Against CHOP Alone in PTCL](https://onco.cc/trials/nct06072131/), [ZEN-3694 with abemaciclib in NUT carcinoma, breast cancer and other solid tumours (NCI phase 1)](https://onco.cc/trials/zen-3694-abemaciclib-nut/), [ZEN-3694 with platinum chemotherapy in NUT carcinoma (NCI phase 1/2)](https://onco.cc/trials/zen-3694-platinum-nut/), [ZEN003694 and Enzalutamide Versus Enzalutamide Monotherapy in Metastatic Castration-Resistant Prostate Cancer](https://onco.cc/trials/nct04986423/)
- people: [Bradley E. Bernstein](https://onco.cc/people/bradley-bernstein/), [Christopher R. Vakoc](https://onco.cc/people/christopher-vakoc/), [Kristian Helin](https://onco.cc/people/kristian-helin/), [Pierre Fenaux](https://onco.cc/people/pierre-fenaux/), [Stephen B. Baylin](https://onco.cc/people/stephen-baylin/), [William G. Nelson](https://onco.cc/people/william-nelson/)
- ideas: [Block the chemical switch that lets cells hide from treatment](https://onco.cc/ideas/idea-bio1-epigenetic-persister-blockade/), [Break up the liquid droplets where oncogenic transcription happens](https://onco.cc/ideas/idea-bio1-condensate-disruptors/), [Eradicate dormant cancer cells: a programme to wake and kill or lock asleep disseminated cells](https://onco.cc/ideas/idea-moon-dormancy-eradication-programme/), [Group trials by broken mechanism, not by organ or single mutation](https://onco.cc/ideas/idea-bio2-mechanism-defined-baskets/), [Keep dormant cells asleep instead of trying to kill them](https://onco.cc/ideas/idea-bio2-pro-dormancy-therapy/), [Switch off an undruggable oncogene permanently with epigenetic editing](https://onco.cc/ideas/idea-bio1-epigenetic-silencing-in-vivo/), [Unmask hidden antigens with a short epigenetic course before immunotherapy](https://onco.cc/ideas/idea-bio2-epigenetic-priming-cold-tumours/)
- pathways: [Cold tumours: immune deserts and exclusion](https://onco.cc/pathways/immune-desert-exclusion/), [Drug-tolerant persister cells](https://onco.cc/pathways/drug-tolerant-persisters/), [Epigenetic reprogramming](https://onco.cc/pathways/epigenetic-reprogramming/), [Lineage plasticity & neuroendocrine transformation](https://onco.cc/pathways/lineage-plasticity-neuroendocrine/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- terms: [Epigenetic progenitor theory: cancer without a first mutation](https://onco.cc/terms/epigenetic-progenitor-theory/), [Gene expression](https://onco.cc/terms/gene-expression/), [Hallmark (2022): non-mutational epigenetic reprogramming](https://onco.cc/terms/nonmutational-epigenetic-reprogramming/), [Hypomethylating agents (azacitidine, decitabine)](https://onco.cc/terms/hma/)
- institutions: [National University Hospital / National University Cancer Institute, Singapore](https://onco.cc/institutions/nuh-ncis/), [Ruijin Hospital, Shanghai Jiao Tong University](https://onco.cc/institutions/ruijin-hospital/), [USC Norris Comprehensive Cancer Center](https://onco.cc/institutions/usc-norris/)
- roadmaps: [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/)

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