HDAC1 (Histone Deacetylase 1)

This robust activity was attributed to a dual mechanism combining immune stimulation and direct antiproliferative effects. These results make 13t a promising cancer immunotherapy drug candidate.

Furthermore, we demonstrated that 8g induced neurite outgrowth and showed good neuroprotective activity in PC-12 cells. Our research provided a new promising structure for the development of HDAC6is against Alzheimer's disease.

In summary, our mechanistic investigations revealed TFAP2C as a novel oncogenic driver in OC and a key regulator of ferroptosis via its epigenetic modulation of the KEAP1-NRF2 axis. These findings highlight TFAP2C as a potential therapeutic target for ferroptosis-inducing therapies in OC patients with high TFAP2C expression.

This study provides a theoretical framework for exploring the molecular mechanisms through which DEP may contribute to CRC development, emphasizing the value of network toxicology in cancer research. These findings may inform future investigations into the risks of DEP exposure and support public health policy and the development of targeted therapeutic strategies.

Then, the hypoxic PASMCs were transfected si-GLI1 alone or together with HDAC1-OE, and further confirm that GLI1 promotes hypoxia induced pyroptosis and abnormal proliferation of PASMCs by upregulating HDAC1 protein expression. In addition, we constructed a PAH rat model, and found that GLI1 silenced PAH rats had reduced expression of markers related to pyroptosis and smooth muscle cell proliferation in the lung tissue, and the lung injury of rats was reduced, and the lung function was significantly improved, suggesting that GLI1 silencing is beneficial to PAH in rats.

Together, these findings suggest that PRAME and ETS2 cooperatively suppress ciliogenesis in melanoma cells, proposing a previously unrecognized epigenetic mechanism of ciliary loss. This mechanism broadens our understanding of melanoma progression and highlights the role of the PRAME-ETS2-HDAC1 axis in regulating ciliogenesis.

Computational ADMET analyses further supported the experimental findings. These findings identify 7a and 7c as potent and selective HDAC6 inhibitors with antiproliferative activity in hematologic tumor cells, highlighting benzodioxol-benzyl hydroxamate hybrids as promising scaffolds for anticancer drug development.

Collectively, our findings suggested that the downregulation of RB1 significantly influences the morphology of LUAD by facilitating EMT and nuclear abnormalities through HDAC1-mediated deacetylation of lamin A/C. Future research should prioritize the development of targeted therapies aimed at restoring RB1 function or inhibiting HDAC1 to mitigate cancer progression, thereby enhancing patient stratification and treatment strategies in TKI-resistant LUAD.

Subsequent SHAP analysis revealed SRC, HSP90AB1, HSP90AA1 and CDK1 as the key contributors to prognostic prediction, with each being highly expressed in BC and linked to poor clinical prognosis. Notably, among all chemicals screened, Disperse Yellow 3 exhibited the strongest binding affinity to these four key targets, demonstrating the strongest association with BC risk.

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.

Pharmacologic inhibition of HDAC1 with panobinostat recapitulated the tumor-suppressive effects observed with MIG-6 overexpression. These findings suggest that HDAC1 may represent a potential therapeutic target in EEC and that HDAC inhibition can attenuate early tumor progression and angiogenic signaling in preclinical models. Implications: This study identifies the MIG-6/HDAC1 axis as a key regulator of angiogenesis in EEC, highlighting HDAC1 inhibition as a promising targeted therapeutic strategy for early tumor suppression.

Motivated by promising clinical trial data for the combination of the histone deacetylase 6 (HDAC6) inhibitor ricolinostat with the proteasome inhibitor bortezomib in relapsed/refractory multiple myeloma (MM) patients, we engineered dual HDAC6/proteasome inhibitors...Deploying the HDAC6-selective phenyl-4-hydroxamic acid motif, and O-carbamoylated hydroxamates as hydroxamic acid surrogates, then grafting to the electrophilic boronic acid warhead of bortezomib/ixazomib, we discovered several dual HDAC6/proteasome inhibitors that were potent in cell-free assays, inhibiting the chymotrypsin-like (CL) proteasomal activity on par with that of bortezomib, and many compounds demonstrated selectivity for HDAC6 over HDAC1 as predicted. Moreover, several dual HDAC6/proteasome inhibitors were submicromolar inhibitors of MM cell growth. Of particular interest, AMC-3-030 with an O-(N-phenylcarbamoyl)-hydroxamate ZBG emerged as an exciting lead for further studies.