pracinostat (SB939)

This study investigates the mechanisms by which histone deacetylase (HDAC) inhibitors induce epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC), focusing on the role of Cathepsin B. Lung cancer cell lines A549 and H1975 were treated with HDAC inhibitors SAHA and SB939, and various assays were conducted to assess cell viability, apoptosis, migration, invasion, and cytoskeletal changes...Cathepsin B was identified as a key mediator of the HDAC inhibitor-induced EMT, which it promotes by interacting with and upregulating the transcription factor Slug. These findings suggest that Cathepsin B is a crucial factor in HDAC inhibitor-induced EMT in NSCLC, indicating that targeting this enzyme may provide a novel therapeutic strategy to counteract invasiveness in lung cancer.

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.

pracinostat activates the p53 signaling pathway by targeting the miR-381-3p/MDM2 axis, thereby inhibiting the proliferation of pancreatic cancer cells. These findings provide novel insights and potential therapeutic strategies for pancreatic cancer, and may also provide a reference for the treatment of other malignancies.

P2, N=208, Active, not recruiting, The Australasian Leukaemia and Lymphoma Group | Recruiting --> Active, not recruiting

Furthermore, MMP2 exhibits crosstalk STAT3 to induce metastasis of breast cancer cells. To conclude, SB939 may be used as a small molecule compound for the clinical treatment of breast cancer.

We identified that histone deacetylases (HDACs) were prominent candidates, and subsequently identified that the HDAC inhibitors mocetinostat and pracinostat, as well as the combined HDAC-epidermal growth factor receptor inhibitor CUDC-101, were effective at radiosensitising cell models of HNSCC (FaDu, A253, UMSCC11b) through their impact on both spheroid growth and clonogenic survival assays. We also demonstrated that this combinatorial strategy leads to inhibition of the repair of DNA double-strand breaks through the neutral comet assay and γH2AX foci analysis using immunofluorescence microscopy, providing a mechanism of action through which HDAC inhibition functions in HNSCC radiosensitisation. We believe that this approach should be further investigated in preclinical models, in order to realise the full therapeutic potential of HDAC inhibition for the radiosensitisation of HNSCC, eventually leading to improved patient treatment efficacy and outcomes.

The relationship between DLBCL and glutathione-related genes was uncovered by our research, and six glutathione genes were linked to DLBCL. These genes might be used as diagnostic biomarkers or targets for treatment for DLBCL patients.

Overall, our results suggest that IDO1 tryptophan metabolites produced by neuronal cells may act on AHR in pathogenic CD4+ T cells in a paracrine fashion in the CNS and that the specific induction of IDO1 expression in neurons at disease-afflicted sites can be considered a therapeutic approach to block the progression of multiple sclerosis without affecting systemic immunity.

A series of novel benzimidazole derivatives were designed and synthesised based on the structures of reported oral available ALK inhibitor and HDAC inhibitor, pracinostat...Compound 3b also inhibited various ALK mutants known to be involved in crizotinib resistance, including mutant L1196M (IC50, 4.9 nM)...At 20 mg/kg, 3b inhibited tumour growth by 85% yet had a negligible effect on mean body weight. These results suggest a attracting route for the further research and optimisation of dual ALK/HDAC inhibitors.

Knockdown of ALDH1A3 prevented HGSOC tumorigenesis and enhanced cell sensitivity to paclitaxel or cisplatin...Treatment of exogenous acetate with NaOAc or inhibition of histone deacetylase with Pracinostat increased H3K27ac and PITX1 levels. CHIP assay demonstrated a significant enrichment of H3K27ac at the PITX1 promoter, and ALDH1A3 knockdown reduced the binding between H3K27ac and PITX1. Taken together, our data suggest that ALDH1A3, transcriptional activated by HIF-1α, promotes tumorigenesis and decreases chemosensitivity by increasing H3K27ac of PITX1 promoter in HGSOC.

AT.9283, EXEL.2280, Gilteritinib, and Pracinostat had the largest correlation (absolute value) with a risk score. Four risk model genes (mRNAs), 12 miRNAs, and 21 lncRNAs formed an mRNA-miRNA-lncRNA network, containing HOXA10-hsa-miR-129-5p-LINC00689 and KIF18A-hsa-miR-221-3p-DANCR. Through bioinformatics, we constructed a prognostic model of m6A-associated anoikis genes in LGG, providing new ideas for research related to the prognosis and treatment of LGG.

The ability of SB939 to sensitize HT-29 cells suggests that SB939 can induce essential changes in cell signaling pathways. Thus, the pan-HDAC inhibitor SB939 sensitizes TRAIL-induced apoptosis via up-regulation of DR5, and SB939-TRAIL combined treatment may target the MAPK pathways and serve as an effective therapeutic strategy against CRC.