PX-478

Furthermore, pharmacological inhibition of HIF1α using PX‑478 abrogated hypoxia‑induced NED and attenuated activation of AKT/mTOR signaling, further underscoring the significance of the miR‑135b‑5p‑HIF1AN‑HIF1α axis in NED of PCa cells. Collectively, the findings of the present study reveal a novel miR‑135b‑5p‑HIF1AN‑HIF1α signaling axis that is involved in hypoxia‑induced NED via AKT/mTOR activation and identify miR‑135b‑5p and HIF1α as potential therapeutic targets for NEPC.

In this investigation, we established a novel NIH/3T3 cell model of asbestos-induced malignant transformation using 3D culture techniques, followed by the development of a corresponding mouse model via orthotopic transplantation. Subsequent administration of the HIF-1α inhibitor PX-478 to both models allowed for the assessment of model reliability through the observation of malignant phenotypes and associated protein alterations.

HIF-1α inhibitor PX478 did not enhance the anti-tumor effects of B+A, but HIF-1α activator DMOG reversed them. In addition, the combination therapy enhanced CD4+ and CD8+ T-cell infiltration and increased pro-inflammatory cytokines. These findings highlight the therapeutic potential of combining anlotinib and bevacizumab for NSCLC treatment and identify HIF-1α as a key target.

YSSX improved MDSC-mediated immunosuppression in a mouse model after chemotherapy by inhibiting the HIF-1α/iNOS-GCN2/eIF2α signaling axis.

Collectively, our results suggested the combination of luteolin and PX-478 to enhance the anticancer effects of PX-478 in breast carcinoma cells by impeding the cell growth and inducing DNA damage response under hypoxia.

Here, we present an innovative in-situ formed fibrin gel-based drug delivery system (PX-478 + αPD-1@Gel), co-loaded with PX-478, a selective hypoxia-inducible factor 1α (HIF-1α) inhibitor, and anti-programmed cell death receptor 1 (αPD-1), for controlled and sequential drug release...Furthermore, the fibrin gel exhibits rapid coagulation and effective hemostasis, reducing intraoperative bleeding and shortening hemostasis time. This dual-functional system, combining localized chemo-immunotherapy with hemostatic properties, shows substantial promise for improving clinical outcomes in glioma patients.

Moreover, co-treatment with Isoquercitrin and the HIF-1α inhibitor PX-478 further suppressed HIF-1α and HO-1 expression, highlighting Isoquercitrin's involvement in modulating the HIF-1α/HO-1 signaling pathway. These findings suggest that Isoquercitrin may ameliorate IR by inhibiting ferroptosis through regulation of the HIF-1α/HO-1 pathway. This study provides promising prospects for the clinical application of active compounds derived from traditional Chinese herbal medicines in IR treatment.

Abnormal activation of the HIF-1α/PPARγ axis may represent a potential mechanism underlying X-ray-induced abnormalities in myocardial energy metabolism and cellular damage. Furthermore, AS-IV has the potential to alleviate radiocardiac injury by modulating energy metabolism and restoring mitochondrial function.

Inhibition of the Hypoxia-inducible factor-1α (HIF-1α)/ B-cell lymphoma-2 interacting protein 3 (BNIP3) pathway by the HIF-1α inhibitor PX-478 intensified cellular damage and reduced the protective effect of BMAL1 overexpression in TCMK-1 cells. These results indicate that BMAL1 regulates mitophagy in diabetic renal I/RI through the HIF-1α/BNIP3 pathway, providing valuable insights for the development of targeted therapies for diabetic renal I/RI.

This work underscores that remodelling the hypoxic TNBC microenvironment can restore the antitumor activity of Vγ9Vδ2 T cell therapy. Our findings offer a compelling new adjuvant strategy to improve the outcomes of Vγ9Vδ2 T cell-based therapies for advanced breast cancer treatment.

Furthermore, PX-478 could suppress the expression of HIF-1α and vascular endothelial growth factor-A (VEGF-A), but BPRC0261 only suppressed VEGF-A. Taken together, this innovative 3D NIR-II imaging system combining the biocompatible Pdots with unique optical specificity enables non-invasive, real-time monitoring the efficacy of anti-angiogenic compounds.

Re-expression of GBE1 in shGBE1 cells alleviated apoptosis and reduced PX-478- induced apoptosis and pathway downregulation. In conclusion, our findings provide convincing evidence that PX-478 induces apoptosis by inhibiting the PI3K/AKT/mTOR pathway through downregulation of GBE1 in AML cells.