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Entinostat is an oral, class I-selective HDAC inhibitor built on a benzamide scaffold; "class I-selective" means it preferentially hits HDAC1, HDAC2, and HDAC3 rather than the whole HDAC family. It has been studied mostly in breast cancer, usually paired with hormonal (anti-estrogen) therapy to try to overcome treatment resistance, and it drew a lot of interest in immuno-oncology because blocking these enzymes can dial down the immune-suppressing cells that let tumors hide. It is an investigational drug; despite encouraging mid-stage results, its big confirmatory breast-cancer trial did not deliver, so it has never reached routine approval.
- Selective for class I HDACs (HDAC1/2/3)
- Oral dosing, unlike some IV HDAC inhibitors
- May resensitize hormone-resistant breast cancer
- Can ease tumor immune suppression
- Fatigue
- Nausea
Mechanism
HDACs remove acetyl groups from histones and other proteins; taking those groups off generally compacts chromatin and quiets genes, so inhibiting HDACs tends to loosen chromatin and switch genes back on, including tumor-suppressor and differentiation programs that cancers keep silenced. Entinostat concentrates on the class I enzymes (HDAC1/2/3) [1], and by re-opening those genes it slows proliferation and nudges cancer cells toward apoptosis (programmed death) [2]. In triple-negative breast cancer models it reversed the epithelial-to-mesenchymal transition (a shape-shift that helps tumor cells spread) and cut back the tumor-initiating "stem-like" cell pool, reducing metastasis in mice [3][4].
A large part of the excitement was immune. inhibition can reduce myeloid-derived suppressor cells and other brakes on the immune system, which is why entinostat was combined with immunotherapy and with anti-estrogens to resensitize resistant tumors [1][2]. On the clinical side, the mid-stage ENCORE 301 study of entinostat added to the aromatase inhibitor exemestane suggested longer progression-free and overall survival, which launched the phase III E2112 registration trial [5]; early-phase work in other populations showed it was tolerable with a manageable, mostly blood-count-related toxicity profile [6]. The catch is the ending: the confirmatory phase III did not confirm the survival benefit, so the mechanism remains scientifically interesting while the drug stalled short of approval.
receptor fingerprint
HDAC1 / HDAC2 / HDAC3 (class I)inhibits (selective)
Tumor cell apoptosis / differentiationpromotes
Myeloid-derived suppressor cellsreduces
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
Entinostat is an investigational anticancer agent, not a supplement or nootropic, and should be treated as a serious drug. In trials its common problems were bone-marrow suppression (low neutrophils and platelets), fatigue, nausea, and occasional heart-rhythm signals; HDAC inhibitors as a class can prolong the QT interval and disturb electrolytes. It has never been approved for general use, and its pivotal breast-cancer trial was negative. There is no legitimate self-administration use case here.
Subjective profileweighing the evidence above
An investigational cancer drug, not a supplement or a nootropic, and its pivotal breast cancer trial was negative. Bone marrow suppression and QT effects come with the HDAC class. There is no legitimate reason for anyone to take this outside a clinical trial.
Resources
This entry is here for reference.
Research
- 2015first citedHistone Deacetylase Inhibitor Entinostat Inhibits Tumor-Initiating Cells in Triple-Negative Bre…
- 2017most active year3 papers
- 2021most recentPhase I Study and Pilot Efficacy Analysis of Entinostat, a Novel Histone Deacetylase Inhibitor,…
- 1.Entinostat for the treatment of breast cancer
- 2.Histone Deacetylase Inhibitors: An Attractive Therapeutic Strategy Against Breast Cancer
- 3.Histone Deacetylase Inhibitor Entinostat Inhibits Tumor-Initiating Cells in Triple-Negative Breast Cancer Cells
- 4.Targeting triple negative breast cancer with histone deacetylase inhibitors
- 5.E2112: randomized phase III trial of endocrine therapy plus entinostat/placebo in patients with hormone receptor-positive advanced breast cancer
- 6.Phase I Study and Pilot Efficacy Analysis of Entinostat, a Novel Histone Deacetylase Inhibitor, in Chinese Postmenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer
6 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
What does 'class I-selective' mean here?
The HDAC family has several classes. Entinostat mostly hits the class I enzymes (HDAC1, 2, 3) rather than the whole family, which is meant to give a cleaner effect than a pan-HDAC drug that blocks everything.
Is entinostat approved?
No. It reached phase III in breast cancer on the strength of a promising mid-stage trial, but the confirmatory study did not show the survival benefit, so it remains investigational.
Why was it combined with immunotherapy?
Blocking HDACs can reduce immune-suppressing cells that shield tumors, so the idea was to pair it with checkpoint inhibitors or hormonal therapy to make resistant cancers respond again.
Could I use it as a nootropic?
No. It is a cytotoxic-class investigational cancer drug with bone-marrow and heart-rhythm risks; there is no cognitive-enhancement use.
Adverse effects
- Fatigue
- Nausea
Notes and cautions
- Low blood counts (neutrophils, platelets)
- Possible QT prolongation / electrolyte shifts