Jingzhuda (entinostat)

P1/2, N=29, Not yet recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

We present a case of a man in his 70s with metastatic melanoma who experienced progression through sequential treatments including pembrolizumab in combination with the HDAC inhibitor entinostat, and ipilimumab. Transdifferentiation has been observed in a wide range of malignancies, but the molecular mechanisms of this phenomenon are poorly understood. This case provides the first molecularly validated example of melanoma to rhabdomyosarcoma transdifferentiation presenting as spatially segregated metastatic lesions with distinct, unmixed histologies and illustrates a mechanism of resistance to immunotherapy driven by phenotypic plasticity.

Among the compounds, domatinostat and entinostat exhibited the strongest affinities (ΔGbind ≈ -70 kcal/mol), in reasonable agreement with experimental data (r = 0.60). This supports an allosteric inhibition mechanism in which ligands lock HDAC3 into inactive conformations. Collectively, these findings offer mechanistic insights into HDAC3 regulation and highlight structural hot spots for the rational design of selective inhibitors with potential applications in targeted breast cancer therapy.

P2, N=50, Not yet recruiting, Sun Yat-sen University

Drug sensitivity analysis suggested therapeutic efficacy of Entinostat and 5-fluorouracil in this subgroup. Our study provides the first LLPS-associated prognostic framework for CRC, offering both a risk stratification tool and actionable therapeutic insights. The findings highlight LLPS as a critical molecular organizer in CRC pathogenesis and a potential target for precision oncology approaches.

P=N/A, N=52, Not yet recruiting, The First Affiliated Hospital of Chongqing Medical University; The First Affiliated Hospital of Chongqing Medical University

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.

P1, N=57, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Sep 2026

MS275 suppresses HCC cell proliferation and induces hepatocyte-like differentiation through PKM1-mediated metabolic reprogramming and ROS signaling. These findings support the potential of MS275 as a differentiation-based therapeutic strategy for HCC.

The expression of USP2 was positively correlated with sensitivity to small-molecule drugs, including entinostat, SB590885, and PF-562,271. USP2 acts as a negative regulator of gastric cancer progression. Consequently, USP2 has the potential to be utilized as a therapeutic target to improve the clinical prognosis and survival rates of patients.

We show evidence of an optimized experimental protocol capable of potentiating the anti-melanoma efficacy of ENT while maintaining a non-cytotoxic profile in non-tumorigenic cells.

Importantly, both compounds displayed the same efficacy in 2D and 3D culture models, and a single treatment with entinostat improved survival in an immunocompetent mouse model compared with fluvastatin and standard cisplatin-pemetrexed chemotherapy, which showed similar anti-tumor effects. Combination of entinostat with anti-PD1 even eradicated tumors in several mice and immunized them against re-transplantation of tumor cells. Overall, the drug sensitivity data provided by this study represents a resource to facilitate future clinical investigations to improve treatment of PM.