mocetinostat (MGCD0103) / Otsuka, BMS - LARVOL DELTA

Enhancement of antigen presentation restores immune recognition in rhabdomyosarcoma (AACR 2026) - "RMS cell lines (n=9) were treated with IFN-γ and clinically relevant drugs, decitabine (DAC), mocetinostat, and tazemetostat. Pediatric tumors show distinct patterns of antigen presentation, such as high MHC-I in alveolar soft part sarcoma and low expression in RMS, though individual tumor subtypes exhibit internal variability. IFN-γ and epigenetic agents restore antigen presentation, including increased NLRC5 expression. Pharmacological treatment and NLRC5 restoration enhanced antigen presentation and sensitized RMS PDX to TCR mediated T-cell cytotoxicity."

IO biomarker • Alveolar Soft Tissue Sarcoma • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • HLA-A • HLA-B • HLA-C • IFNG • NLRC5 • PRAME

EXPRESS: Mocetinostat (MGCD0103) induced autophagy in SKBR-3 breast cancer cells by regulating ROS/MAPK pathway. (PubMed, J Investig Med) - "Mocetinostat suppressed the growth of breast cancer cells in vitro through a ROS-mediated autophagy mechanism using the MAPK pathway. Investigating the mechanism of mocetinostat may provide a novel therapeutic approach for breast cancer treatment."

Journal • Breast Cancer • Oncology • Solid Tumor • ATG5

Simultaneous single-cell proteomics and epigenetic analysis of histone deacetylase inhibition in human cells. (PubMed, Commun Biol) - "To this end, I applied SCP to the analysis of cancer cells treated with mocetinostat, a class specific histone deacetylase inhibitor...While other techniques exist to measure histone modifications in single human cells, the approach presented here allows simultaneous quantification of hundreds of proteins, allowing phenotypic insight as well as epigenetic inferences in each individual cell. All raw and processed data described in this study has been made publicly available through the ProteomeXchange/MASSIVE repository system as MSV000093434."

Journal • Oncology

A Biomimetic Photothermal Nanoplatform for Epigenetic-Driven Tumor Immunotherapy and Immune Memory Induction. (PubMed, ACS Appl Mater Interfaces) - "GS@AM@M exhibits excellent photothermal conversion efficiency under NIR-II (808 nm) irradiation, while its mesoporous framework enables efficient coloading of the DNA methyltransferase inhibitor 5-azacytidine (5-Aza) and the histone deacetylase inhibitor mocetinostat (MGCD). This synergistic mechanism effectively eradicates both primary and metastatic tumors while establishing durable immune memory to prevent recurrence. By integrating photothermal therapy, immunotherapy, and epigenetic modulation, GS@AM@M provides a potent and precise platform for comprehensive breast cancer treatment."

Journal • Breast Cancer • Gene Therapies • Oncology • Solid Tumor • CD8

Antifibrotic Efficacy of Daclatasvir Against Pulmonary Fibrosis: Insights From Network Pharmacology, Molecular Docking, Dynamics, and Preclinical Evaluations. (PubMed, Chem Biodivers) - "The present study evaluated DAC in a bleomycin (BLM)-induced PF rat model, integrating network pharmacology, molecular docking, and molecular dynamics (MD) simulation to decipher its mechanisms...PCA analyses also confirmed complex stability, comparable to known inhibitors vorinostat and mocetinostat...Interestingly, a higher dose (12.4 mg/kg/day) showed reduced efficacy and increased lung index, indicating dose sensitivity. These findings suggest that DAC possesses dose-dependent antifibrotic activity in PF and warrants further exploration as a repurposable therapeutic candidate."

Journal • Preclinical • Fibrosis • Hepatitis C • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • HDAC2 • HIF1A

HDAC inhibitors restore osteoimmune balance and bone regeneration via selective MAPK modulation in inflammatory bone disease. (PubMed, Stem Cell Res Ther) - "TSA, PXD, and MGCD function as dual-action therapeutics by regulating macrophage polarization and enhancing osteogenesis, thereby establishing a pro-regenerative microenvironment and reversing inflammatory bone loss. These findings provide mechanistic insight into the epigenetic control of immune-bone crosstalk and support a drug-repurposing strategy that utilizes clinically available HDAC inhibitors to accelerate the development of osteoimmunomodulatory therapies."

Journal • Gene Therapies • Inflammation • Orthopedics • Osteoporosis

ZEB1 promotes chemo-immune resistance in pancreatic cancer models by downregulating chromatin acetylation of CXCL16. (PubMed, J Clin Invest) - "ZEB1 knockdown synergized with gemcitabine and anti-PD1 therapy, markedly suppressed PC growth, and prolonged survival in vivo. Importantly, the epigenetic inhibitor Mocetinostat (targeting ZEB1) potentiated chemoimmunotherapy efficacy, including anti-PD1 and CAR-T therapies, in patient-derived organoids, xenografts, and orthotopic models. Our study unveils ZEB1 as a master epigenetic regulator of chemoimmunotherapy resistance and proposes its targeting as a transformative strategy for PC treatment."

IO biomarker • Journal • Preclinical • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • CXCL16 • GZMA • SPP1 • ZEB1

Clinical Experience with HDAC Inhibitor-Based Protocols in MECOM-Rearranged Acute Myeloid Leukemia (SOHO 2025) - "Regimens included valproic acid (n = 3), vorinostat (n = 3), mocetinostat (n = 2), and panobinostat (n = 1). HDAC inhibitor-based regimens achieved an encouraging ORR of 67% in MECOMr-AML. These findings support further investigation of HDAC-targeted approaches in this high-risk molecular subset."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • HDAC3 • MECOM

Pembrolizumab (Immunotherapy Drug) in Combination With Guadecitabine and Mocetinostat (Epigenetic Drugs) for Patients With Advanced Lung Cancer. (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2025 ➔ Jul 2026 | Trial primary completion date: Jul 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Mocetinostat With Vinorelbine in Children, Adolescents & Young Adults With Refractory and/or Recurrent Rhabdomyosarcoma (clinicaltrials.gov) - P1 | N=38 | Active, not recruiting | Sponsor: Jonsson Comprehensive Cancer Center | Recruiting ➔ Active, not recruiting | Trial completion date: May 2026 ➔ May 2027 | Trial primary completion date: May 2025 ➔ May 2026

Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor

CLINICAL EXPERIENCE WITH HDAC INHIBITOR-BASED PROTOCOLS IN MECOM-REARRANGED ACUTE MYELOID LEUKEMIA (EHA 2025) - "Patients received protocols incorporating valproic acid (n=3), vorinostat (SAHA, n=3), mocetinostat (n=2), and panobinostat (n=1).Nine patients (1%) with MECOMr were identified (median age 57 years, range 16-76). We observed a 67% response rate with HDAC inhibitor-based therapy, suggesting a potential benefit of HDAC inhibition in MECOMr-AML. Although limited by small sample size and heterogeneous HDAC inhibitor regimens, these findings warrant further investigation through dedicated clinical trials to define optimal use of HDAC inhibition strategies in this therapeutically challenging leukemia subgroup with poor prognosis and limited treatment options."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Pneumonia • Respiratory Diseases • HDAC3 • MECOM

Heart Failure Treatment in Underserved Populations: A Comprehensive Analysis of Sacubitril/Valsartan and Sodium-Glucose Transporter 2 Inhibitor (SGLT2i) Prescription Trends at a Safety Net Hospital. (PubMed, Cureus) - "Results Of the 769 patients prescribed sacubitril/valsartan, 497 (64.6%) were prescribed the 24 mg/26 mg dose, 193 patients (25.1%) received the 49 mg/51 mg dose, and 79 patients (10.3%) were on the 97 mg/103 mg dose...Regarding SGLT2is, 2,287 patients were prescribed these medications: 343 patients were prescribed dapagliflozin (188 at the 5 mg dose and 155 at the 10 mg dose); one patient received ertugliflozin at the 5 mg dose; 634 patients were prescribed canagliflozin (404 at the 100 mg dose, 173 at the 300 mg dose, 40 at the 50 mg dose with metformin combination, and 17 at the 150 mg dose with metformin combination); and 1,309 patients were prescribed empagliflozin (972 at the 10 mg dose, 333 at the 25 mg dose, two at the 5 mg dose with metformin combination, and two at the 12.5 mg dose with metformin combination)...Conclusions Robust evidence supports the use of sacubitril/valsartan and SGLT2is in HF, with both also proving effective for treating other diseases..."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Design, synthesis, and biological evaluation of N-(2-amino-phenyl)-5-(4-aryl- pyrimidin-2-yl) amino)-1H-indole-2-carboxamide derivatives as novel inhibitors of CDK9 and class I HDACs for cancer treatment. (PubMed, Bioorg Chem) - "The cellular assays revealed that 13ea induced mitochondria-related apoptosis and G2/M phase arrest in cancer cells, showing superior activities compared to those of AZD-5438 (a CDK9 inhibitor) and Mocetinostat (an inhibitor of class I HDACs). Notably, the in vivo assay demonstrated that 13ea (30 mg/kg) exhibited significant inhibition on MDA-MB-231 xenograft tumor growth, with a tumor shrinkage rate of 76.83 %. In summary, we have identified 13ea as a novel CDK9/HDAC inhibitor with excellent anticancer activity in vitro and in vivo."

Journal • Oncology • CDK9 • HDAC1 • HDAC3

Unraveling SMARCA1's role in cancer progression, drug resistance, and muscle differentiation through EMT-related signaling, TGF-β pathway, and key transcription factors SNAI1 and EGR1 (AACR 2025) - "Further cell survival assays revealed that SMARCA1 KO cells are particularly sensitive to the HDAC2 inhibitor Mocetinostat and the MEK inhibitor Trametinib, proposing that targeting SMARCA1 in combination with HDAC2 or MEK inhibition could be an effective therapeutic approach for RMS...Additionally, SMARCA1 KO cells responded differently to both canonical and non-canonical TGF-β pathway inhibitors, including SB505124 (TGFBR1 inhibitor), the PI3K-mTOR inhibitor Dactolisib, and Withaferin A (NF-κB inhibitor). Notably, these TGF-β pathway inhibitors effectively overcame resistance in ARMS cells with SMARCA1 expression, exposing specific vulnerabilities in these otherwise resistant cells. Together, our findings suggest that targeting both canonical and non-canonical TGF-β pathways, alongside SMARCA1, presents promising therapeutic strategies for overcoming drug resistance and potentially limiting RMS progression."

Oncology • Rhabdomyosarcoma • Sarcoma • Solid Tumor • CDK4 • EGR1 • HDAC2 • MYCN • Myogenin • NFKB2 • PPP2R5C • PTEN • SMARCA4 • SMARCD3 • SNAI1 • TGFB1 • TGFBR1

Developmental states determine intrinsic resistance to immunotherapy in pediatric rhabdomyosarcoma [WITHDRAWN] (AACR 2025) - "Epigenetic drugs targeting DNA methylation (decitabine), EZH2 (tazemetostat), Class I/IV HDACs (mocetinostat), and LSD1 (GSK-LSD1) were used at sub-cytotoxic doses on RMS cell lines (n=10). RMS cell lines, PDXs, and tumors exhibited a range of MHC-I expression, with most having low or undetectable surface expression. Exome sequencing of RMS tumors did not detect frequent genomic alterations in the APM pathway genes. The state of development in RMS tumors was associated with the APM gene signature and surface MHC-I expression with dominant myoblast cell states negatively correlating with APM."

Clinical • IO biomarker • Tumor mutational burden • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • CD8 • PRAME • TMB

High throughput drug screening on head and neck cancer organoids reveals novel therapeutic strategies (COSM 2025) - "Of these, 4 exhibited ≥ 50% selectivity for tumor tissue compared to normal (pracinostat, tanespimycin, SB-743921, and mocetinostat). High-throughput drug screening across eight normal, dysplastic, and HNSCC PDOs revealed protein and epigenetic targeting drugs to have the most proportional hits. Specifically, HSP90 and HDAC inhibitors were most effective within their drug class. Pending dose response experiments and validation across a larger cohort, these results provide potential novel protein and epigenetic targeting strategies as promising approaches in HNSCC."

Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDC37 • HSP90AA1

Bioequivalence Study to Compare Sacubitril and Valsartan Tablets (97mg/103mg) Versus Entresto® (Sacubitril and Valsartan) Tablets (97 mg/103 mg) (clinicaltrials.gov) - P1 | N=48 | Completed | Sponsor: Humanis Saglık Anonim Sirketi

New P1 trial • Cardiovascular • Heart Failure

Sp4/HD11 and Sp1/HAT-p300 complexes induce apoptotic cell death in CuCl2-treated neurons by modulating histone acetylation on BCL-W and BAX promoters. (PubMed, Neurochem Int) - "Herein, we found that CuCl2 (300μM in SH-SY5Y cells or 100μM in cortical neurons) determined apoptotic cell death, that was counteracted by the class IV HDs inhibitor Mocetinostat (MOCE) and by the HAT-p300 inhibitor C646, but not by the class I and II HDs inhibitors...Importantly, while the single knocking-down of Sp1, Sp4, HD11 and HAT-p300 partially mitigated CuCl2-induced cell death, the double-transfection of siRNAs for Sp1 and Sp4, or for HD11 and HAT-p300, completely reverted the neurotoxic effect of CuCl2. Collectively, we found that CuCl2-induced neuronal apoptosis is determined by the binding of Sp1/HAT-p300 and of Sp4/HD11 transcriptional complexes on the BAX and BCL-W gene, respectively, unraveling a new pathway involved in Copper-induced neurotoxicity."

Journal • BAX • BCL2L2

Comprehensive Investigation of a Tyrosine Kinase Inhibitor-Resistant Gene Zeste White 10 in Hepatocellular Carcinoma. (PubMed, World J Oncol) - "Mocetinostat and capecitabine were predicted to be the potential inhibitors targeting ZW10 with a minimum binding energy of -8.2 and -7.1 kcal/mol, respectively. ZW10 is considered a TKI-resistant and tumor-supportive gene, which is also a promising novel prognostic biomarker for HCC or a therapeutic target for overcoming TKI resistance."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor

High throughput drug screening on head and neck cancer organoids reveals novel therapeutic strategies (AHNS-COSM 2025) - "Of these, 4 exhibited ≥ 50% selectivity for tumor tissue compared to normal (pracinostat, tanespimycin, SB-743921, and mocetinostat). High-throughput drug screening across eight normal, dysplastic, and HNSCC PDOs revealed protein and epigenetic targeting drugs to have the most proportional hits. Specifically, HSP90 and HDAC inhibitors were most effective within their drug class. Pending dose response experiments and validation across a larger cohort, these results provide potential novel protein and epigenetic targeting strategies as promising approaches in HNSCC."

Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CDC37 • HSP90AA1

CLU/PROK2 in chronic Hepatitis B: an exploratory study on its role as a potential diagnostic biomarker and therapeutic target with persistent positive in HBV DNA level receiving entecavir treatment (APASL 2025) - "Molecular docking and virtual screening pinpointed Camostat mesylate, c- Kit-IN-1, and Mocetinostat as the top drug candidates for targeting CLU and PROK2. Elevated CLU and PROK2 levels are associated with an increased risk of CHB, and this enzyme is notably overexpressed in CHB patients' serum and liver tissues. CLU and PROK2 could potentially act as a diagnostic biomarker, providing new avenues for diagnosing and treating CHB. Table and Figure:Figure 1.Figure 3."

Biomarker • Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Glomerulonephritis • Hepatitis B • Hepatology • Infectious Disease • Inflammation • Nephrology • Renal Disease • CTSS • ITGB3

Focal adhesion kinase drives proliferation and invasion in gastrointestinal neuroendocrine tumours via modulation of transformative cell signalling and gene expression (ENETS 2025) - "FAK inhibition was achieved with Protac-FAK and Y15, while Mocetinostat was used to inhibit histone deacetylases (HDACs)...CONCLUSION Our findings indicate that FAK is involved in both cell signalling and gene expression regulation in GI-NETs. Further studies are needed to explore FAK's potential as a therapeutic target for GI-NETs."

Endocrine Cancer • Gastrointestinal Disorder • Neuroendocrine Tumor • Oncology • Solid Tumor • Targeted Protein Degradation • KDR

Proteomic analysis reveals chromatin remodeling as a potential therapeutical target in neuroblastoma. (PubMed, J Transl Med) - "Mocetinostat and clofarabine offer valuable insights for the development of novel targeted therapies in neuroblastoma."

Journal • CNS Tumor • Ganglioneuroblastoma • Neuroblastoma • Oncology • Solid Tumor • ALYREF • ARID1A • ARID1B • BRD2 • BRD3 • PBRM1 • SF3B1 • SMARCA4 • SMARCA5 • TP53BP1

HDAC Inhibitors Can Enhance Radiosensitivity of Head and Neck Cancer Cells Through Suppressing DNA Repair. (PubMed, Cancers (Basel)) - " We identified that histone deacetylases (HDACs) were prominent candidates, and subsequently identified that the HDAC inhibitors mocetinostat and pracinostat, as well as the combined HDAC-epidermal growth factor receptor inhibitor CUDC-101, were effective at radiosensitising cell models of HNSCC (FaDu, A253, UMSCC11b) through their impact on both spheroid growth and clonogenic survival assays. We also demonstrated that this combinatorial strategy leads to inhibition of the repair of DNA double-strand breaks through the neutral comet assay and γH2AX foci analysis using immunofluorescence microscopy, providing a mechanism of action through which HDAC inhibition functions in HNSCC radiosensitisation. We believe that this approach should be further investigated in preclinical models, in order to realise the full therapeutic potential of HDAC inhibition for the radiosensitisation of HNSCC, eventually leading to improved patient treatment efficacy and outcomes."

Journal • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

EXPRESS: Investigation of the synergic effect of mocetinostat and capecitabine in a triple-negative breast neoplasms mouse model. (PubMed, J Investig Med) - "Tumor weights were also reduced by 21% in the mosetinostat group, 27.5% in the capecitabine group and 45% in the combined group. The combination of mocetinostat and capecitabine decreased the formation of tumors and metastases in lung tissue.In summary, the combination of mocetinostat and capecitabine was more effective than either drug alone in reducing the size of triple-negative breast neoplasms in a mouse model."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer