HDAC4 (Histone Deacetylase 4)

Mechanistically, HIT211504993 inhibits Myc-driven tumorigenesis by promoting nucleocytoplasmic acetylation and modulating p53, cell-cycle, and Wnt/β-catenin signaling. The investigation of antitumor activity and its mechanism of action provides a theoretical basis for the development of the next-generation benzenesulfonanilide HDAC inhibitors.

SAHA imposes a common anti-proliferative core but engages distinct lineage-conditioned risk modules in LUAD and LUSC-cell-cycle/migration-linked in LUAD and checkpoint/stress-linked in LUSC. These SAHA feature-sensing modules provide a mechanistic and clinically anchored framework for subtype-tailored HDAC-directed combinations and for future development of HDACi-aligned biomarkers in NSCLC.

HDAC inhibition represents a viable strategy against hypoxia-driven metastasis. Future work should optimize selective inhibitors, develop predictive biomarkers, and explore natural compound derivatives to enhance efficacy and reduce toxicity.

Our findings identify a self-reinforcing NAT10/HDAC4 signaling circuit that drives breast cancer progression and immune evasion. Targeting NAT10 represents a promising therapeutic strategy to overcome immunosuppression and improve patient outcomes in breast cancer.

Additionally, a higher throughput thermal shift format was developed using dot blot analysis. Thermal shift analysis offers a useful complement to enzyme activity assays for characterization of HDAC inhibitors.

SB939 treatment raised CXCR3 expression by 2.4 times and CD8+ infiltration by 39%. These findings point to HDAC4 as a crucial epigenetic regulator of immune cell trafficking in lung cancer. Given the growing interest in ultrasound-assisted medication delivery and immunological priming, our findings point to HDAC4 as a viable therapeutic target in ultrasound-guided immunomodulatory methods for lung cancer.

We then summarize the recent medicinal chemistry efforts, from the class-selective deacetylase inhibitors to the recently emerged targeted protein degraders that not only achieve superior isoform selectivity but also modulate HDAC7's deacetylase-independent functions. By bridging the functional complexity of HDAC7 with the latest advances in chemical biology tools, we aim to provide a timely summary of the current status of HDAC7 as a druggable target and offer a perspective on strategies guiding the development of next-generation modulators.

Moreover, it suppressed β-catenin expression, unlike NBDHEX; however, it retained GSTP1 inhibitory potency, indicating its add-on therapeutic potential. Therefore, NHSe-2 could be a potential anticancer agent and can be considered for further analysis for its multimodal activity in the realm of cancer research in the future.

Intriguingly, administration of the histone deacetylase inhibitor trichostatin A resulted in the upregulation of CYP3A5 expression...Because ESCC develops, CYP3A5 suppression promotes tumor metastasis and invasion. CYP3A5 is a potential biomarker and therapeutic target for ESCC.

Imaging Mass Cytometry (IMC) reveals no significant changes in immune cells, but a notable shift in the distribution patterns of cancer-associated hepatic stellate cells in the metastatic niche, when YAP is ablated in the cancer cells. The results demonstrate a novel metastasis-driving cell signaling pathway mediated by the functional interaction between HDAC4 and MybL1, which regulates YAP expression and metastasis.

5-Fluorouracil (5-FU) remains the most commonly used first-line chemotherapeutic agent for the treatment of esophageal cancer (EC), but its therapeutic efficacy is unsatisfactory...We screened our drug library and found that HDAC4/5/6/7 inhibitor TMP269 and BRD2/3/4 inhibitor ABBV-744 showed potent synergistic cytotoxic effects with 5-FU in the parental ESCC cells...Animal experiments further demonstrated that YFF-702 significantly improved the efficacy of 5-FU in an in vivo tumor model. This current research demonstrates that combining HDAC/BET inhibition with 5-FU may be a promising therapeutic strategy for ESCC patients by targeting 5-FU indued DTP cells.

FB2 also reduced the rate of microtubule regrowth in cells; however, we are unable to conclude whether this is due to direct binding to tubulin or to some indirect mechanism involving initial interaction with some other target sites. These effects on tubulin dynamics are likely responsible for defects in spindle structure, mitotic arrest, and the observed robust killing of cancer cells.