Jingzhuda (entinostat)

Specifically, the high-risk group exhibited increased immune cell infiltration, lower IC50 values for several drugs including 5-fluorouracil, afatinib, crizotinib, cediranib, taselisib, and staurosporine; Whereas the low-risk group displayed reduced stromal component proportions and better responses to entinostat, irinotecan, KRAS inhibitors, cisplatin, axitinib, and topotecan. The lactylation-m6A related prognostic model exhibited robust predictive efficiency in HCC. TCOF1 and HDAC1 may be promising tumor biomarkers for HCC and more researches are needed to validate these results.

In vivo, we confirmed that entinostat treatment increased the expression of immunecheckpoint ligands and antigen presentation machinery in Myc-driven tumors in a Rb1/Trp53/MycT58A (RPM) SCLC mouse model, while shifting tumors from a neuroendocrine (NE)-high to a NE-low phenotype, and was associated with increased T-cell infiltration Notably, combining entinostat with anti-PD-1 immunotherapy suppresses tumor growth and significantly prolonged survival in RPM allograft models. These findings underscore the potential of entinostat to reprogram the NE status of SCLC, enhance immune checkpoint blockade efficacy, and improve therapeutic outcomes.

Comparative pathway analysis identified preferential de-repression of a G2/M checkpoint gene program in 105C spheroids upon Entinostat treatment when compared directly to the KOC-7c spheroids. Our results suggest that the utility of HDACi in OCCC is highly context-dependent.

Exploratory drug-response modeling with pRRophetic suggested lower estimated half-maximal inhibitory concentration (IC50) values for agents including MS-275 (entinostat), PF-4708671, and roscovitine in the high-risk group. The TIDE algorithm carries prognostic information in NSCLC beyond immunotherapy settings. The proposed TIDE-informed gene signature reproduced prognostic stratification across cohorts, suggesting potential applicability to a broader NSCLC population and supporting future personalized risk stratification.

Murine and human MDSC models treated with Entinostat revealed that the long non-coding RNA Malat1 downregulates pSTAT3 and decreases MDSC-mediated suppression of T cell proliferation...Collectively, our findings provide a multi-pronged mechanism of HDAC inhibition in MDSCs that inform the development of future rational combination therapies. HDAC1 inhibition in MDSCs increases Malat1 , decreases pSTAT3, induces apoptosis/cell cycle arrest, and decreases suppression of T cells.

Our findings reveal an epigenetic-Hippo-immunomodulatory axis in osteosarcoma that also extends to other sarcomas, providing a rationale for incorporating epigenetic preconditioning with immunotherapy to improve patient outcomes and pointing towards novel biomarkers for treatment guidance.

Leveraging scaffold hopping and structural optimization strategies, we developed fifteen indole-based derivatives utilizing vorinostat (SAHA) and entinostat as lead compounds. Mechanistic investigations of representative hydroxamate and benzamide derivatives corroborated their marked antiproliferative effects in HCT-116 cancer cells and manifested a favorable safety profile against the normal fibroblasts (WI-38). Altogether, these findings underscore the therapeutic potential of the identified potent compounds for combating cancer via HDAC1/6 inhibition.

P2, N=60, Recruiting, Hebei Medical University Fourth Hospital

In vivo, Entinostat suppressed tumor growth and consistently modulated the HDAC1/p53/AMPK/mTOR pathway. In conclusion, Entinostat exerts potent anti-tumor activity in SCLC by simultaneously inducing apoptosis and autophagy through epigenetic modulation of p53 via HDAC1 inhibition and subsequent regulation of the AMPK/mTOR axis.

A2780ADR cells revealed cross‑resistance to multiple compounds, including anticancer drugs [cisplatin (CisPt) and etoposide (Eto)] and DNA repair/DNA damage response (DDR) inhibitors (olaparib, niraparib, entinostat, prexasertib and rabusertib). However, combination treatment with Doxo and Ver also increased the cytotoxic response of non‑malignant murine cardiomyocytes, murine embryonic stem cells and human induced pluripotent stem cells. Taken together, the present study suggested inhibition of MDR1‑mediated Doxo efflux by Ver a useful approach to overcome acquired drug resistance of A2780ADR cells by stimulating DDR‑related cytotoxicity, yet at the price of a potentially increased risk of normal tissue toxicity.

P1/2, N=47, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2026 --> Feb 2027

Nine compounds significantly activated Wnt signaling, including antivirals (imidocarb, proflavine, aminoacridine), anticancer agents (entinostat, enzastaurin, abemaciclib), and GSK-3β inhibitors (BIO, CP21R7). In mice, aminoacridine-especially combined with minoxidil-showed the strongest hair regrowth, while proflavine and imidocarb enhanced nail elongation. These results reveal new therapeutic candidates for hair and nail regeneration.