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Last update 25 Nov 2025

Entinostat

Last update 25 Nov 2025

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Entinostat (JAN/USAN/INN), N-(2-aminophenyl)-4-(N-(pyridin-3-ylmethoxycarbonyl)aminomethyl)benzamide, N-[[4-[(2-aminoanilino)-oxomethyl]phenyl]methyl]carbamic acid 3-pyridinylmethyl ester

+ [13]

Target

HDACs

Action

inhibitors

Mechanism

HDAC inhibitors(Histone deacetylase inhibitors), Epigenetic drug

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesImmune System Diseases+ [3]

Active Indication

Hormone receptor positive HER2 negative breast cancerBreast CancerMetastatic melanoma+ [4]

Inactive Indication

Adenocarcinoma of prostateAdvanced breast cancerAdvanced cancer+ [45]

Originator Organization

Bayer AG

Active Organization

Merck Sharp & Dohme Corp.

Syndax Pharmaceuticals, Inc.

EOC Pharma (Thaizhou) Co., Ltd.

Inactive Organization

AstraZeneca PLC

Kyowa Kirin Co., Ltd.

Bristol Myers Squibb Co.

+ [2]

License Organization

Syndax Pharmaceuticals, Inc.

Kyowa Kirin Co., Ltd.

Eton Pharmaceutical (China) Co., Ltd.

+ [1]

Drug Highest PhaseApproved

First Approval Date

China (24 Apr 2024),

Hormone receptor positive HER2 negative breast cancer

RegulationOrphan Drug (European Union)

Structure/Sequence

Molecular FormulaC21H20N4O3

InChIKeyINVTYAOGFAGBOE-UHFFFAOYSA-N

CAS Registry209783-80-2

Clinical Trials associated with Entinostat

NCT07235618

/ Not yet recruitingPhase 2IIT

A Phase II, Two-Stage Study Evaluating the Efficacy of Entinostat in Combined With Fulvestrant in Locally Advanced or Metastatic Breast Cancer With Recurrence or Progression After CDK4/6 Inhibitor Plus Endocrine Therapy

This study aims to evaluate the efficacy of Entinostat combined with Fulvestrant in HR+/HER2- advanced breast cancer patients with recurrence/progression after endocrine therapy (primary endpoint: progression-free survival [PFS]), and explore the correlation between peripheral blood mononuclear cell (PBMC) acetylation levels and treatment response to determine the baseline acetylation threshold .

Start Date05 Jan 2026

Sponsor / Collaborator

Sun Yat-Sen University

ChiCTR2500107234

/ Not yet recruitingPhase 2IIT

A single-arm, prospective, phase II clinical study of the combination of entinostat and oral paclitaxel in the treatment of HR+HER2- advanced breast cancer

Start Date01 Sep 2025

Sponsor / Collaborator

Tianjin Medical University Cancer Institute and Hospital

[+1]

ChiCTR2500108694

/ Not yet recruitingNot ApplicableIIT

Prospective intervention study of entinostat + azacitidine +CHOP in the treatment of nodal follicular helper T cell lymphoma

Start Date01 Aug 2025

Sponsor / Collaborator

The Second Affiliated Hospital of Chongqing Medical University

[+2]

100 Clinical Results associated with Entinostat

100 Translational Medicine associated with Entinostat

100 Patents (Medical) associated with Entinostat

1,379

Literatures (Medical) associated with Entinostat

31 Dec 2025·REDOX REPORT

MS-275 facilitates osseointegration in osteoporotic rats by mitigating oxidative stress via activation of the miR-200a/Keap1/Nrf2 signaling pathway

Article

Author: Chen, Yuhu ; Yan, Junjie ; Guan, Wengang ; Chen, Bin ; Jiang, Wenkai ; Yang, Min ; Gu, Qinsong ; Zhou, Zhi ; Li, Jianqiao

OBJECTIVES:

Osteoporosis, a prevalent metabolic bone disease affecting millions worldwide. Although MS-275 has been reported to inhibit oxidative stress, its ability to protect osteoblasts from oxidative stress damage has yet to be clarified. This study investigated whether MS-275 can inhibit oxidative stress and promote osteogenesis by activating the miRNA-200a/Keap1/Nrf2 signaling pathway.

METHODS:

In vitro, MC3T3-E1 cells underwent induction with carbonyl cyanide 3-chlorophenylhydrazone, leading to the establishment of an oxidative stress model, investigating the underlying mechanism. In vivo, using a rat model of ovariectomized osteoporosis, evaluating the effects of MS-275.

RESULTS:

In vitro, MS-275 treatment of oxidation-induced MC3T3-E1 cells resulted in up-regulation of osteoblast protein, increased expression of miRNA-200a, increased binding of miRNA-200a to Keap1 mRNA, decreased expression of Keap1 protein, and dissociation of Nrf2 from Keap1. The expressions of total Nrf2, nuclear Nrf2 and HO-1 were increased, mitochondrial function was enhanced, and oxidative damage was reduced. However, these effects were reversed after interference with miRNA-200a. In vivo,MS-275 effectively enhanced the microstructural features of distal femoral trabecular bone, increased the mineralization capacity of osteoblasts, and promoted bone formation.

DISCUSSION:

MS-275 can reverse oxidative stress-induced cell damage, promote bone healing, and improve osteoporosis by activating the miRNA-200a/Keap1/Nrf2 pathway.

31 Dec 2025·JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

Development of novel benzamide class I selective lysine deacetylase inhibitors as potent anticancer agents

Article

Author: Sellars, Jonathan D. ; Gill, Jason H. ; Waddell, Paul G. ; Shnyder, Steven D. ; Fishwick, Colin W. G. ; Grigg, Ronald

Small molecule inhibitors of lysine deacetylases (KDACs), exemplified by histone deacetylases (HDACs), exhibit significant promise as cancer therapeutics. Using a modular combinatorial chemistry approach, a novel class of KDAC inhibitors (KDACi) containing the aminophenyl-benzamide headgroup have been developed, which incorporate a vinyl group within the linker region for active site stabilisation and a trifluoromethyl moiety within the capping group to exploit enzyme surface topology. Consequently, a class I selective KDACi (7) with a preference towards HDAC1 over other class I KDACs was identified. This KDACi orientates differently within the KDAC active site and exhibits an improved antitumour profile relative to the benchmark class I selective KDACi Entinostat (1). The clinical potential of 7 is further exemplified by the inhibition of tumour growth in an in vivo model of ovarian cancer. These results offer significant scope for the rational development of KDACi with improved selectivity against specific KDAC and widespread therapeutic potential.

01 Dec 2025·BREAST

Investigating the prognostic role of citrullination-related genes in breast cancer by combining transcriptomics, single-cell analysis and verification

Article

Author: He, Weijie ; Li, Yuehua ; Fan, Shanji ; Yi, Xinyu ; Luo, Yongmei ; Liu, Yingjie ; Li, Zhimin ; He, Guicheng

Citrullination, a process linked to autoimmune diseases, has been implicated in cancer, but its role in breast cancer (BRCA) remains unclear. This study aimed to identify citrullination-related genes (CRGs) associated with prognosis in BRCA. We utilized datasets from The Cancer Genome Atlas (TCGA-BRCA) and Gene Expression Omnibus (GEO), pinpointing candidate genes by intersecting differentially expressed genes (DEGs) from TCGA-BRCA with known CRGs. Prognostic CRGs were selected using univariate Cox regression and Lasso regression analyses, and a predictive nomogram was created based on independent prognostic factors identified through multivariate Cox regression. Our findings revealed that SEZ6, S100B, SPIB, and TFF1 were key CRGs used to construct a risk model. High-risk BRCA patients exhibited immune-suppressive tumor microenvironments (TMEs) with low CD8⁺ T cell mutation and enrichment in C1/C4 immune subtypes. In contrast, low-risk patients displayed high immune infiltration and enrichment in C2/C3/C6 subtypes. High expression of S100B, SPIB, and TFF1 was associated with increased immune infiltration by NK cells and T cells, while high SEZ6 expression was linked to neutrophil mutations, PD-L1 upregulation, and low CD8⁺ T cell infiltration. Molecular docking studies explored the interactions of these CRGs with entinostat. In conclusion, SEZ6, S100B, SPIB, and TFF1 were identified as significant prognostic genes in BRCA, providing insights into BRCA pathogenesis and potential personalized treatment strategies.

News (Medical) associated with Entinostat

20 Aug 2025

·www.prnewswire.com

HDAC Inhibitors Market Sees Upward Trajectory Across the 7MM During the Forecast Period (2025-2034) Driven by Innovation in Cancer Therapies | DelveInsight

The HDAC inhibitor pipeline remains active, with several next-generation agents advancing in clinical trials. Abexinostat (Xynomic Pharmaceuticals) is in Phase III development for renal cell carcinoma, representing a potential expansion into solid tumors. Quisinostat (Viriom) is in Phase II for uveal melanoma, and Entinostat, partnered between EOC Pharma and Syndax, is being explored in Hodgkin lymphoma. LAS VEGAS, Aug. 20, 2025 /PRNewswire/ -- DelveInsight's HDAC Inhibitors Market Size, Target Population, Competitive Landscape & Market Forecast report includes a comprehensive understanding of current treatment practices, addressable patient population, which includes top indications such as Multiple Myeloma, Peripheral T-cell Lymphoma (PTCL), Cutaneous T-cell Lymphoma (CTCL), Amyotrophic Lateral Sclerosis (ALS), and others. The selected indications are based on approved therapies and ongoing pipeline activity. The report also provides insights into the emerging HDAC inhibitors, market share of individual therapies, and current and forecasted market size from 2020 to 2034, segmented into 7MM. Key Takeaways from the HDAC Inhibitors Market Report As per DelveInsight's analysis, the total market size of HDAC inhibitors in the 7MM is expected to surge significantly by 2034. The report provides the total potential number of patients in the indications, such as Multiple Myeloma, Peripheral T-cell Lymphoma (PTCL), Cutaneous T-cell Lymphoma (CTCL), Amyotrophic Lateral Sclerosis (ALS), and others. Leading HDAC inhibitor companies, such as Xynomic Pharmaceuticals, Viriom, EOC Pharma, Syndax Pharmaceuticals, Jubilant Therapeutics, and others, are developing novel HDAC inhibitors that can be available in the HDAC inhibitors market in the coming years. Some of the key HDAC inhibitors in the pipeline include Abexinostat, Quisinostat, Entinostat, JBI-802, and others. Discover which indication is expected to grab the major HDAC inhibitors market share @ HDAC Inhibitors Market Report HDAC Inhibitors Overview Histone deacetylases (HDACs) remove acetyl groups from both histone and non-histone proteins. Because acetylation of histones is linked to an open chromatin structure and active gene transcription, HDAC activity leads to histone deacetylation and epigenetic suppression of gene expression. Since HDACs influence many pathways involved in cancer development, HDAC inhibitors (HDACis) show clinical effects through several mechanisms, including changes in gene expression of cell cycle and apoptotic proteins, acetylation of other proteins involved in cell growth and survival, effects on angiogenesis, aggresome formation, and DNA repair. There are 18 known HDACs, divided into two major groups and four classes based on their cellular location, homology, enzyme mechanism, sequence of discovery, and histone substrate specificity. The first group includes zinc-dependent HDACs, which all share a similar catalytic core for deacetylating acetyl-lysine residues. These comprise Class I (HDAC1, -2, -3, -8), Class II (IIa: HDAC4, -5, -7, -9; IIb: HDAC6, -10), and Class IV (HDAC11). The second group includes Class III HDACs (sirtuins, SIRT1–7), which rely on NAD+ for their enzymatic activity. HDAC Inhibitors Epidemiology Segmentation The HDAC inhibitors market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM, segmented into: Total Cases of Selected Indications for HDAC Inhibitor Total Eligible Patient Pool of Selected Indications for HDAC Inhibitor Total Treated Cases of Selected Indications for HDAC Inhibitor HDAC Inhibitors Treatment Market Several HDAC inhibitors are currently available on the market. Recent entrants include DUVYZAT (givinostat), while earlier approved drugs include BELEODAQ (belinostat), HIYASTA (tucidinostat), among others. DUVYZAT is a histone deacetylase inhibitor approved for treating Duchenne muscular dystrophy (DMD) in patients aged 6 and above. While it is categorized as an HDAC inhibitor, its exact mechanism of action in DMD is not fully understood. In April 2025, Italfarmaco announced that the CHMP of the European Medicines Agency (EMA) issued a positive opinion on DUVYZAT. The drug is also being evaluated in other indications: Phase III trial in Becker muscular dystrophy (BMD) and Phase II trial in polycythemia vera. HIYASTA (HBI-8000) is an epigenetic immunomodulator approved for several indications, including use as monotherapy for certain subtypes of relapsed or refractory T-cell non-Hodgkin's lymphoma, specifically adult T-cell leukemia-lymphoma (ATLL) and peripheral T-cell lymphoma (PTCL) in Japan. HUYABIO International is conducting a multinational Phase III trial evaluating HIYASTA in combination with nivolumab for previously untreated metastatic or unresectable malignant melanoma. HIYASTA is an oral HDAC Class I inhibitor that induces cell cycle arrest and apoptosis in tumor cells, which underlies its efficacy in lymphoma. In September 2020, the Japanese Ministry of Health, Labour and Welfare (MHLW) granted orphan drug designation (ODD) to HIYASTA for relapsed/refractory ATL, and in December 2015 for PTCL. In June 2021, HUYABIO also received regulatory approval in Japan for HBI-8000 as monotherapy for relapsed/refractory ATL. Key Emerging HDAC Inhibitors and Companies Xynomic Pharmaceuticals (Abexinostat), Viriom (Quisinostat), EOC Pharma/Syndax Pharmaceuticals (Entinostat), Jubilant Therapeutics (JBI-802), and several other companies are currently engaged in the development and production of HDAC inhibitors, which have the potential to significantly impact and enhance the HDAC inhibitors market. Abexinostat, an oral, broad-spectrum HDAC inhibitor originally developed by Pharmacyclics and later licensed by Xynomic Pharmaceuticals in 2017, has demonstrated encouraging activity in both blood cancers and solid tumors. The drug is currently being studied in several Phase I to III clinical trials worldwide. In September 2019, Xynomic announced that the FDA had granted Fast Track Designation (FTD) to abexinostat as a monotherapy for fourth-line treatment of relapsed or refractory follicular lymphoma. The FDA had previously granted FTD for abexinostat in combination with pazopanib for first- or second-line therapy in renal cell carcinoma. Additional Phase II trials are underway in indications such as Diffuse Large B-cell Lymphoma (DLBCL) and Follicular Lymphoma. Quisinostat is another potent, selective oral pan-HDAC inhibitor, initially developed by Janssen Pharmaceuticals. HDAC inhibitors work by inducing cell cycle arrest, promoting differentiation, and triggering apoptosis in various human cancer cell lines. By inhibiting histone deacetylase, they increase acetylation of histone proteins, resulting in a more transcriptionally active chromatin state and altered gene expression involved in proliferation, apoptosis, and differentiation. Multiple preclinical studies and Phase I/II trials have evaluated quisinostat's safety and effectiveness, showing promising anti-tumor effects in several advanced and treatment-resistant cancers — including platinum-resistant ovarian cancer (in combination with paclitaxel and carboplatin), uveal melanoma, and synovial sarcoma. The anticipated launch of these emerging therapies are poised to transform the HDAC inhibitors market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the HDAC inhibitors market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. To know more about HDAC inhibitors clinical trials, visit @ HDAC Inhibitors Treatment Recent Developments in the HDAC Inhibitors Space In May 2025, Amylyx Pharmaceuticals announced positive Week 48 data from the Phase II open-label HELIOS clinical trial of AMX0035 in adults living with Wolfram syndrome. In May 2025, the University of Miami, in collaboration with Viriom, initiated a Phase II clinical trial in the US (NCT06932757) to evaluate an oral therapy for patients with uveal melanoma who have undergone at least one prior line of treatment. In April 2025, Xynomic Pharmaceuticals concluded a Phase I/II clinical trial in the United States (NCT03939182), evaluating a combination oral therapy for patients with Diffuse Large B-cell Lymphoma and Mantle Cell Lymphoma who had received at least one prior line of treatment. Discover more about HDAC inhibitors in development @ HDAC Inhibitors Clinical Trials HDAC Inhibitors Market Dynamics HDAC inhibitors are a class of epigenetic drugs that modify gene expression by altering chromatin structure. Initially developed as anticancer agents, they have shown significant therapeutic potential in various malignancies, especially hematologic cancers like T-cell lymphoma and multiple myeloma. The market initially gained traction with FDA approvals of drugs such as Vorinostat, Romidepsin, and Panobinostat. Their unique mechanism of action targeting epigenetic regulation drew interest as precision medicine and oncology research grew, driving pharmaceutical investment in this segment. The HDAC inhibitors market continues to expand largely due to the rising prevalence of cancer worldwide and the need for more targeted therapies with better safety profiles. Additionally, ongoing clinical trials are exploring HDAC inhibitors in combination with other therapies, such as immune checkpoint inhibitors, proteasome inhibitors, and traditional chemotherapeutics. These combination approaches aim to overcome resistance and enhance efficacy, creating more opportunities for market growth. As more data emerges demonstrating synergistic benefits, partnerships between biotech startups and large pharmaceutical firms are accelerating further development. Despite this positive outlook, the market faces several challenges. Many HDAC inhibitors are associated with toxicity issues such as fatigue, gastrointestinal disturbances, and thrombocytopenia, which limit broader adoption. Competition from newer targeted therapies and immuno-oncology drugs also puts pressure on the HDAC inhibitor segment. Moreover, several compounds failed in late-stage trials due to a lack of efficacy, leading to cautious investor sentiment and prioritization of combination rather than monotherapy approaches. Looking ahead, the market dynamics are expected to be shaped increasingly by precision oncology trends and biomarker-driven patient selection, allowing more effective targeting of responders. If safety profiles can be improved and combination regimens continue to show strong results, HDAC inhibitors will retain a meaningful role in the evolving oncology landscape. Novel formulations, selective HDAC isoform inhibitors, and expansion into non-oncology indications such as neurodegenerative or inflammatory diseases may further diversify the market and drive its next phase of growth. Learn more about the HDAC inhibitors @ HDAC Inhibitors Analysis Scope of the HDAC Inhibitors Market Report HDAC Inhibitors Therapeutic Assessment: HDAC Inhibitors' current marketed and emerging therapies HDAC Inhibitors Market Dynamics: Conjoint Analysis of Emerging HDAC Inhibitor Drugs Competitive Intelligence Analysis: SWOT analysis and Market entry strategies Unmet Needs, KOL's views, Analyst's views, HDAC Inhibitors Market Access and Reimbursement Table of Contents Related Reports Multiple Myeloma Market Multiple Myeloma Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key multiple myeloma companies, including Sanofi, Karyopharm Therapeutics, Takeda Pharmaceutical, Celgene, Bristol-Myers Squibb, RAPA Therapeutics, Pfizer, Array Biopharma, Cellectar Biosciences, BioLineRx, Celgene, Aduro Biotech, ExCellThera, Janssen Pharmaceutical, Precision BioSciences, Takeda, Glenmark (Ichnos Sciences SA), Poseida Therapeutics, Molecular Partners AG, Chipscreen Biosciences, AbbVie, Genentech (Roche), Janssen Biotech, Nanjing Legend Biotech, Merck Sharp & Dohme Corp., among others. 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Cutaneous T-cell Lymphoma Market Cutaneous T-cell Lymphoma Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key CTCL companies, including Pfizer, Helsinn Therapeutics, Kyowa Hakko Kirin, Citius Pharmaceuticals, Soligenix, Prescient Therapeutics, Innate Pharma, Bristol-Myers Squibb, BioInvent International AB, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Phase 2Phase 3Fast TrackOrphan DrugImmunotherapy

22 Nov 2024

·www.drugs.com

Entinostat + Nivolumab Yields Durable Results in Some Pancreatic Cancer Patients

FRIDAY, Nov. 22, 2024 -- Combination treatment with entinostat and nivolumab results in durable responses in a small subset of patients with advanced pancreatic ductal adenocarcinoma (PDA), according to a study published online Nov. 12 in Nature Communications . Marina Baretti, M.D., from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University in Baltimore, and colleagues combined entinostat and nivolumab in patients with advanced PDA in a phase 2 study. A 14-day lead-in of entinostat 5 mg orally once weekly was followed by entinostat and nivolumab treatment. Twenty-seven evaluable patients were enrolled between November 2017 and November 2020. The researchers found partial responses in three patients (objective response rate, 11 percent), with a median response duration of 10.2 months. Median progression-free survival was 1.89 months and overall survival was 2.729 months. Nineteen patients (63 percent) had grade ≥3 treatment-related adverse events, including reduced lymphocyte count, anemia, hypoalbuminemia, and hyponatremia. Entinostat yielded increases in dendritic cell activation and maturation. In a small subset of PDA patients, entinostat and nivolumab showed durable responses, although the primary end point was not met. "This study creates a roadmap for this strategy, and future areas of exploration include additional mechanistic studies that will lead to combinatorial approaches, both preclinically and clinically, to expand the subset of patients that could benefit from an histone deacetylase inhibitor-based immunomodulatory strategy," the authors write. Several authors disclosed ties to biopharmaceutical companies, including Syndax, which manufactures entinostat and supplied the study medications. Abstract/Full Text Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.

Phase 2Clinical Result

22 Feb 2024

·www.fiercebiotech.com

A SMRT new target for male contraceptives works in mice

The drug works by targeting a component of the process that turns sperm stem cells into sperm. A drug with a past life as a potential anti-cancer agent might someday have a new job as "the pill" for men, new data in mice suggest. In a journal article published Feb. 20 in Proceedings of the National Academy of Sciences, researchers at the Salk Institute explained how they discovered that an oral HDAC inhibitor called entinostat acts like an “off-on” switch for sperm creation that keeps male mice from reproducing without any effect on their libido. Within 60 to 90 days of stopping the pill, the mice were able to impregnate female animals again without any harm to the resulting offspring. Effective male contraceptives are a long time coming, senior author Ronald Evans, Ph.D., told Fierce Biotech Research in an interview. Researchers have been trying for decades to develop a noninvasive, reversible, easily accessible drug candidate that is as effective as the birth control pill is for women, with no success so far. “Our game-changing or transformative results are that it’s now possible to have a male equivalent of the pill that’s able to give men control as well, without having to rely on condoms,” Evans said. (Of course, this wouldn’t eliminate the need for condoms—they’re still necessary to protect against some types of sexually transmitted disease.) Sperm production is a complex process with many components, a limiting factor in coming up with drugs to block it. Hormonal candidates, such as the drug DMAU, have mainly focused on blocking testosterone—a route that varies in effectiveness depending on the patient population and can come with side effects. A non-hormonal injectable drug called RISUG is making its way through clinical trials in India, and a version called Vasalgel is in development in the U.S. However, both of these require either an injection or an in-office procedure. One non-hormonal mechanism that scientists have long considered is blocking receptors for retinoic acid, a form of vitamin A that is critical to the process whereby sperm stem cells differentiate into fully functional sperm. But while this does stop sperm production in mice and rats, it comes at a cost: Retinoic acid is needed for a wide range of processes throughout the body, so inhibiting its activity systemically can lead to serious side effects, Evans explained. “You can kind of get it to work the way you want, but it’s not specific enough to be a useful way to address the challenge of controlling spermatogenesis,” he said. Researchers have largely abandoned the effort in favor of other approaches. But in the new study, Evans’ lab—which was the first to clone the receptor for retinoic acid—learned that there’s another way to go about blocking its role in sperm production without systemic effects. While studying a gene regulatory factor called SMRT, one of the researchers in his lab pointed out that it was part of a complex of proteins that were involved in regulating retinoic acid receptors in sperm creation. “He suggested that maybe we should actually not target the retinoic acid receptor itself, but target SMRT,” Evans recalled. Not only would doing so be easier than targeting the receptor directly, but it would also be safer because the target’s systemic effects are more limited, he added. This led the team to see if blocking SMRT with entinostat, which Evans co-developed under his former company Syndax, would be a solution, as SMRT’s function is controlled by the same components that are interrupted by HDAC inhibitors. They gave male mice one of three different doses of the drug once a day for 60 days, then tested their ability to mate. They also tested whether taking mice off the drug would restore sperm production—and whether it would affect the health of their offspring. To their surprise, the approach was a success. “[The researcher] came back and said, ‘It really works.’ I said, ‘What do you mean it really works?’” Evans recalled. “He said, ‘It’s a total contraceptive. The mice’s libido is totally normal. And if you take it away, [their ability to reproduce] comes back.’” None of the mice that were on the drug sired offspring during the treatment period, compared to litters of around 10 pups each from control males. Sixty days after stopping the treatment, mice in the experimental groups were able to impregnate females again to the same degree as controls. All of the pups were born healthy. During the treatment period, the researchers noticed that the animals’ testis size was “dose-dependently reduced” as their sperm production capacity fell. This was mostly recovered after 60 days off the drug, figures in the article showed. There were no other discernible side effects, such as weight loss that would indicate a change in testosterone levels, the researchers wrote in their paper. “As a proof of principle, our findings indicate that chronic, oral administration of MS-275 transiently blocks male fertility without permanently affecting reproductive capacity or the genomic integrity of sperm,” they wrote. Evans now hopes to test entinostat as a male contraceptive in larger animals and eventually in humans. The drug already has FDA breakthrough status for advanced breast cancer and has been studied in clinical trials for pancreatic cancer, brain cancer, melanoma and other cancers, so safety in humans has already been established, he said. Given the results, Evans’ team has no plans to look at whether other HDAC inhibitors have birth control potential as well, he said, though they might look at other medical uses for entinostat. But for now, its use as a male contraceptive “is at the top of the list,” he said. “That’s where we want to focus and see if there is a company that wants to actually develop this. Or do we have to start our own?” Evans, a serial biotech entrepreneur, said. “That’s kind of fun to think about.”

Clinical Result

100 Deals associated with Entinostat

External Link

KEGG	Wiki	ATC	Drug Bank
D09338	Entinostat	L01XX64	DB11841

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Hormone receptor positive HER2 negative breast cancer	China	EOC Pharma (Thaizhou) Co., Ltd.	24 Apr 2024

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Advanced breast cancer	Phase 3	China	EOC Pharma (Thaizhou) Co., Ltd.	15 May 2018
Hormone receptor positive breast cancer	Phase 3	China	EOC Pharma (Thaizhou) Co., Ltd.	15 May 2018
Breast Cancer	Phase 2	China	Syndax Pharmaceuticals, Inc.	30 Jan 2022
Metastatic Renal Cell Carcinoma	Phase 2	United States	Bristol Myers Squibb Co.	31 Jul 2018
Metastatic Renal Cell Carcinoma	Phase 2	United States	Syndax Pharmaceuticals, Inc.	31 Jul 2018
Renal Cell Carcinoma	Phase 2	United States	Syndax Pharmaceuticals, Inc.	24 May 2018
Uveal Melanoma	Phase 2	Sweden	Merck Sharp & Dohme Corp.	21 Feb 2018
Uveal Melanoma	Phase 2	Sweden	Syndax Pharmaceuticals, Inc.	21 Feb 2018
Metastatic Cholangiocarcinoma	Phase 2	United States	Syndax Pharmaceuticals, Inc.	06 Nov 2017
Metastatic Cholangiocarcinoma	Phase 2	United States	Bristol Myers Squibb Co.	06 Nov 2017

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03978624 (LCCC1827, ASCO2025)	Phase 2	Muscle Invasive Bladder Urothelial Carcinoma Neoadjuvant cisplatin-ineligible	20	Pembrolizumab 200mg IV	zrzovupims(qepqxedekm) = veqwaagynd vwoxwbpayv (lijpytmpvm ) View more	Positive	30 May 2025
				Pembrolizumab 200mg IV + Entinostat 5mg po	zrzovupims(qepqxedekm) = klkdxkreef vwoxwbpayv (lijpytmpvm ) View more
NCT03024437 (CTgov)	Phase 1/2	Neoplasm Metastasis \| Advanced Renal Cell Carcinoma \| Bone metastases	31	Atezolizumab+Bevacizumab+Entinostat (Phase I - Dose Escalation)	qvrngcfrfw = ucsookpxlu plbvzgksul (muspvqpfqx, xftyyguxkn - wtgrlsmych)	-	20 Mar 2025
				Atezolizumab+Bevacizumab+Entinostat (Phase II - Cohort A)	ttadjhvqlg = yxmdjfhntm jmxkybfyvm (dozaoaqkxt, gtnkxdfbwb - dwjludqyrs) View more
NCT02437136 (ENCORE 601 \| ENCORE-601, CTgov)	Phase 1/2	Microsatellite instability-high colorectal cancer \| Melanoma \| Non-Small Cell Lung Cancer ... View more	191	pembrolizumab+entinostat (Phase 2, Cohort 1: Entinostat 5 mg Weekly + Pembrolizumab)	hrrrozswka = dfgiruydnt izoorbzpfs (mgttrxvdsj, aghvuoteyo - iumicppyes) View more	-	20 Mar 2025
				pembrolizumab+entinostat (Phase 2, Cohort 2: Entinostat 5 mg Weekly + Pembrolizumab)	hrrrozswka = qskgxjmxmf izoorbzpfs (mgttrxvdsj, jegdnzgert - haqaqnfccn) View more
NCT03250273 (Pubmed) Manual	Phase 2	Metastatic Pancreatic Ductal Adenocarcinoma	27	Entinostat + nivolumab	kkyepqgwym(buptxsvtjv) = fpthtgjggl xxvtqltyhv (lloqfigmqw, 2.4% - 29.2) Not Met View more	Negative	12 Nov 2024
NCT02936752 (CTgov)	Phase 1	Myelodysplastic Syndromes	28	Pembrolizumab+Entinostat (Treatment (Entinostat, Pembrolizumab) Dose Level 1)	chngwaajor = fhyrfshdba beyalbbomp (nzudkxlszu, tmipvtezlo - tnoymfhwzm) View more	-	01 Oct 2024
				Pembrolizumab+Entinostat (Treatment (Entinostat, Pembrolizumab) Dose Level 2)	chngwaajor = yavqbpyuzo beyalbbomp (nzudkxlszu, cycnvjwbtd - qpfgoqxwbd) View more
NCT03552380 (CTgov)	Phase 2	Metastatic Renal Cell Carcinoma \| Renal Cell Carcinoma	12	Ipilimumab+Nivolumab+Entinostat (Phase II, Dose Level 1:Entinostat 5 mg With Nivolumab and Ipilimumab)	tertpmqpvr = lvczklonzs ivrghkmity (zzbsvdjxbz, neeiovtuoo - lnpdmxrhsl) View more	-	03 Sep 2024
				Ipilimumab+Nivolumab+Entinostat (Phase II, Dose Level 2: Entinostat 3 mg With Nivolumab and Ipilimumab)	tertpmqpvr = wbkbvzcwjv ivrghkmity (zzbsvdjxbz, iwqonqakdw - lbjuyayqjl) View more
NCT03538171 (ASCO2024) Manual	Phase 3	Hormone receptor positive HER2 negative breast cancer HER2 Negative \| HR Positive	354	Entinostat + exemestane	ocvzqibzwp(bfrimuiruz) = xbaejyqltq trdpfhiber (bfeyphmous ) View more	Positive	24 May 2024
				Placebo +exemestane	ocvzqibzwp(bfrimuiruz) = pobmkqvauy trdpfhiber (bfeyphmous ) View more
NCT01928576 (NA_00084192, CTgov)	Phase 2	metastatic non-small cell lung cancer	143	Nivolumab+Entinostat+Azacitidine (ARM A)	zysoiklysr = rrpmawtjds nxbnqyzzly (fcpvyjooku, vxyxunzkyf - ogjjgowsfg) View more	-	03 May 2024
				Nivolumab+CC-486 300 (ARM B)	zysoiklysr = dgbmstustk nxbnqyzzly (fcpvyjooku, wcwsrvbfao - uxdgerryyg) View more
AACR2024 Manual	Phase 2	Pancreatic Ductal Adenocarcinoma	27	EntinostatEntinostat 5 mgnivolumab	jkppxjtyjw(ggxyzgqrda) = orznmxtdhb yolvjouicg (swlfpjiwmx ) View more	Positive	05 Apr 2024
NCT03765229 (CTgov)	Phase 2	Metastatic melanoma	11	Pembrolizumab+Entinostat	kamyegsgkf = lioylmpdwj azxshugqmi (jjbfvvrfbt, mpvnczitkk - gpwxhxqbdt) View more	-	10 Jan 2024

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