P2, N=92, Recruiting, The First Affiliated Hospital of Soochow University | Trial primary completion date: Sep 2024 --> Sep 2025

Meanwhile, Entinostat treatment increased the serum level of the active form (intact) Fgf23 and reduced that of Pi and calcium (Ca) as well. This study raised a concern about the anabolic effects of Entinostat in bone, and demonstrated that Entinostat treatment causes hypophosphatemia and hypocalcemia by upregulating Fgf23 mRNA and increasing intact Fgf23 protein in serum.

P2, N=44, Recruiting, Zhejiang Cancer Hospital | Not yet recruiting --> Recruiting

Compound 20c effectively modulated the expression of biomarkers associated with LSD1 and HDAC inhibition and demonstrated superior antiproliferative activity compared to SAHA and 4SC-202 across multiple colorectal cancer cell lines...It demonstrated significantly enhanced antitumor efficacy compared to SAHA, without causing observable toxicity. These findings highlight the potential of LSD1/HDAC dual inhibitors for the treatment of malignant cancers.

P2, N=51, Recruiting, Fudan University | Trial completion date: Sep 2025 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026

P2, N=42, Recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=30, Not yet recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P2, N=26, Not yet recruiting, ChongQing university cancer hospital; ChongQing university cancer hospital

P2, N=57, Recruiting, Cancer Hospital Chinese Academy of Medical Sciences; Cancer Hospital Chinese Academy of Medical Sciences

P2, N=44, Not yet recruiting, Zhejiang Cancer Hospital

To evaluate the efficacy of a novel histone deacetylase inhibitor, chidamide, in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (CR-CHOP) in the treatment of DEL. The most common grades 3-4 hematologic and nonhematologic toxicity were leukopenia (46.7%) and infection (21%), respectively. This long-term follow-up study indicates that CR-CHOP in untreated DLBCL with the DEL phenotype demonstrates high short-term efficacy and safety as well as promising survival outcomes.

P=N/A, N=25, Not yet recruiting, Peking University People's Hospital

Chidamide combined with (+)-JQ-1 can inhibit the proliferation of MLL-r AML cells, inhibit the initiation of protective self-repair of these leukemia cells by inhibiting the DNA damage response pathway, and ultimately increase the apoptosis of these cells, but non- MLL-r AML cells have no similar results.

P1, N=93, Recruiting, Shanghai Junshi Bioscience Co., Ltd. | Not yet recruiting --> Recruiting

Our study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.

These findings demonstrate that ERAP1 inhibition combined with HDACi entinostat treatment and PD-1 blockade remodels the immune landscape of a non-immunogenic tumor such as NB, making it responsive to checkpoint immunotherapy.

P2, N=76, Recruiting, Ruijin Hospital | Trial primary completion date: Jun 2024 --> Jun 2025

P=N/A, N=400, Not yet recruiting, Ruijin Hospital

In this study, by conducting bioinformatics analyses as well as in vitro and in vivo experiments, we identified that NUSAP1 was significantly upregulated in LUAD, with a notable correlation with poorer overall survival, higher scores for immunogenicity and immune infiltration, as well as increased sensitivity to conventional chemotherapeutic drugs such as paclitaxel, docetaxel and vinorelbine in LUAD. Furthermore, we identified entinostat as a novel inhibitor of NUSAP1. Pharmacological targeting ERβ/NUSAP1 axis with fulvestrant (ERβ antagonist) or entinostat (novel NUSAP1 inhibitor) significantly reduced LUAD growth both in vitro and in vivo, which may represent effective alternative therapeutic strategies for patients with LUAD.

Our study demonstrated that Epi might be used as a HDAC1 inhibitor. Low-dose Epi could inhibit tumor progression by inducing cell ferroptosis in vitro and in vivo. Thus, Epi administration with lower concentration may be much more favorable and safer in the treatment with leukemia.

By adapting a low-cost colorimetric activity assay, we measured low-micromolar IC50 values for these compounds against a humanized construct of zebrafish HDAC10 (A24E-D94A HDAC10). Selected inhibitors were cocrystallized with A24E-D94A zebrafish HDAC10 and zebrafish HDAC6 to provide insight into class IIb isozyme affinity and selectivity.

The triple combination of entinostat, a BETi, and cisplatin is highly synergistic, reverses cisplatin resistance, and may thus serve as a novel therapeutic approach for bladder cancer.

Among them, compound 20 exhibited potential inhibitory activity on HDAC1, and demonstrated notable potency against RPMI-8226 cells with an IC50 value of 2.89 ± 0.43 μM, which was better than chidamide (IC50 = 10.23 ± 1.02 μM)...The ADME parameters calculation showed that 20 possesses remarkable theoretical drug-likeness properties. Taken together, these results suggested that 20 is worthy of further exploration as a potential HDAC-targeted anticancer drug candidate.

P2, N=30, Recruiting, Shanxi Province Cancer Hospital

Further, the cell death was more pronounced with SAHA treatment. Therefore, polydatin might be a better anticancer drug and can have a potential to replace SAHA in combinational therapeutic regimen.

18A possessed similar HDAC inhibitory activity as MS-275 and potently suppressed CDC25 activity in vitro and the CDK1 dephosphorylation in cells. Additionally, 18A hindered the progression of S and G2/M phases, triggered DNA damage, and induced apoptosis. These findings underscore the potential of 18A as a targeted therapy for TNBC and warrants further preclinical development.

Finally, we showed that T cells contribute to in vivo tumor growth control in the presence of entinostat and trametinib combination treatment. Together, our findings reveal that HDAC3 is a druggable endogenous repressor of T cell recruitment into Kras mutant lung tumors.

Results of alamarBlue assay demonstrated that MS-275 and analogs significantly (p < 0.001) reduced viability of MT-2 cells in hypoxic condition. Findings of the present study hold promise for developing new drugs targeting hypoxia-induced changes in ATL.

Moreover, the hydrazide derivatives 5 and 6 showed strong synergism with cisplatin (combination indices <0.2), again outperforming entinostat, and increased DNA damage, p21, and pro-apoptotic BIM expression, leading to caspase-mediated apoptosis and cell death. Thus, compounds 5 and 6 represent promising lead structures for developing new HDACi capable of reversing chemoresistance in cisplatin resistant cancer cells.

P2, N=30, Recruiting, The First Affiliated Hospital of Xiamen University | Trial completion date: Jan 2026 --> Jun 2027 | Trial primary completion date: Jan 2024 --> Jan 2026

P2, N=55, Completed, HUYABIO International, LLC. | Phase classification: P2b --> P2 | N=40 --> 55

P=N/A, N=184, Recruiting, Institute of Hematology & Blood Diseases Hospital, China | Not yet recruiting --> Recruiting

P=N/A, N=30, Recruiting, First affiliated hospital of Soochow university; First affiliated hospital of Soochow university

P2, N=52, Not yet recruiting, the First affiliated hospital of Soochow university; the First affiliated hospital of Soochow university

P2, N=32, Recruiting, First affiliated hospital of Soochow university; First affiliated hospital of Soochow university | Not yet recruiting --> Recruiting | Phase classification: PN/A --> P2 | N=90 --> 32 | Initiation date: Jan 2024 --> Aug 2024

Our findings demonstrate that alternative splicing of STAT3 can be regulated by a compound, providing an important clue for understanding the regulation mechanisms of the expression balance of STAT3 isoforms in a chemical biology approach. Entinostat is likely to be a promising seed compound for elucidating how the higher ratio of STAT3β expression impacts on biological responses associated with Janus kinase (JAK)/STAT3 signaling pathway.

P1, N=57, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Aug 2024 --> Sep 2025

P2, N=23, Completed, HUYABIO International, LLC. | Phase classification: P2b --> P2

Importantly, tumor growth inhibition by HDAC inhibition was dependent on SULF1 expression in CAFs, and CRC patients with more SULF1+ CAFs were more responsive to treatment with the HDAC inhibitor chidamide. Collectively, these findings unveil the critical role of SULF1+ CAFs in CRC and provide a strategy to stratify CRC patients for HDAC inhibitor treatment.

FOLR1 expression was upregulated by VPA, apicidin, and trichostatin A, but downregulated by MS-275 after 24 h treatment. By contrast, HDAC inhibitors exert different regulatory effects on folate carriers. Moreover, HDAC1/2 inhibition may be a potential mechanism involved in altering FOLR1 and SLC46A1 levels.

Here we report chidamide maintenance therapy after allo-HSCT in patients with SET-NUP214 fusion positive T-ALL. Both patients improved effectively during follow-up, confirming the efficacy of chidamide in improving the condition of these patients and may provide valuable clinical information for the treatment of this rare and understudied disease.

P2, N=12, Terminated, Roberto Pili | N=18 --> 12 | Trial completion date: Aug 2023 --> Feb 2024 | Active, not recruiting --> Terminated; Funder halted development of compound in this disease