napabucasin (BBI608)

Notably, Napabucasin effectively inhibited ovarian cancer metastasis in vivo. Collectively, our findings elucidate a previously unrecognized mechanism by which EZH2 governs metastatic progression through cholesterol metabolic rewiring and propose Napabucasin as a promising therapeutic strategy for ovarian cancer, particularly in tumors with EZH2 hyperactivation.

Our findings revealed a signalling pathway in which lung adenocarcinoma regulates stemness and tumourigenesis through HES1, and the targeting of this pathway by VR23 or napabucasin supports further preclinical development for CDK4/6 inhibitor combination therapy.

Notably, SHN7 exerted strong in vivo anti-tumor effects relative to napabucasin and SAHA, with minimal toxic effects. Therefore, SHN7 may be a promising NQO1/STAT3/HDAC triple-target agent that can decrease the resistance of TNBC to HDAC inhibitors and can be developed as a candidate anti-TNBC drug.

These effects were effectively reversed by the stemness inhibitor Napabucasin...In summary, this study reveals that PMN-MDSCs can activate the STAT3-CXCL5-ERK positive feedback regulatory axis via exosomal S100A9, synergistically enhancing breast cancer cell stemness and metastatic capacity. These findings provide a theoretical reference and potential intervention targets for targeting the tumor microenvironment to inhibit TNBC progression.

These findings demonstrate that BBI608 effectively inhibits MEC cell proliferation in vitro by inducing Mcl-1-dependent apoptosis. This suggests BBI608 warrants further investigation as a potential therapeutic agent for MEC.

These findings establish a mechanistic rationale for the concurrent targeting of the MDM2 and STAT3 axes and provide preclinical evidence for a promising, non-genotoxic therapeutic strategy in p53-functional CLL. A limitation of this study is the lack of in vivo validation and clinical data, which are necessary to further assess the safety, optimal dosing, and efficacy, particularly in elderly or unfit patients with limited treatment options.

YZ-35 exhibited remarkable antiproliferative activity across multiple breast cancer cell lines and selectively suppressed BCSC self-renewal, outperforming TTI-101 and matching BBI-608 in potency. In vivo, YZ-35 achieved approximately 90% tumor growth inhibition (10 mg/kg) in xenograft models, with reduced toxicity versus paclitaxel. Mechanistic studies confirmed STAT3 pathway disruption and BCSC depletion. These results highlight YZ-35 as a natural product-derived STAT3 inhibitor with dual antitumor and anti-CSC activity, offering a translational strategy for refractory BRCA.

Brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate, has shown significant efficacy in CD30-positive lymphoma. To address this, we conducted high-throughput screening (HTS) and identified auranofin and napabucasin as synergistic agents that enhance the efficacy of BV. These findings not only highlight the advantages of FCM for CD30 detection, but also provide valuable insights into combination strategies to optimize the therapeutic potential of BV.

Consistent with the results from 2D culture, BBI608 showed effective anticancer effects against OSCC spheroids in 3D culture. These results suggest that BBI608 effectively inhibits STAT3 activation in both 2D and 3D models, offering a promising therapeutic strategy and supporting its potential for repurposing in patients with OSCC who exhibit elevated STAT3 activity.

The objective of the present study was to examine the inhibitory impacts of three antitumor drugs (olmutinib, napabucasin and ponatinib) on the metabolism of cariprazine, and the molecular docking of cariprazine and ponatinib in relation to CYP3A4 was also evaluated. Molecular docking studies had demonstrated that both cariprazine and ponatinib could engage in hydrophobic interactions with residue PHE-304 on CYP3A4. Consequently, when ponatinib is employed in conjunction with cariprazine in a clinical setting, it is imperative to assess the efficacy and adverse effects, and adjust the dosage to attain the optimal efficacy.

The tumor analyses demonstrated clear downregulation of CSC-related biomarkers such as OCT4, SOX2, CD133 and pSTAT3 as well as PSMA by Acupa-mICG-Nap. Rational formulated micellar indocyanine green and napabucasin plus NIR appears as an appealing strategy to co-ablate cancer cells and CSCs with rapid tumor de-bulking yet no recurrence.

In vivo, napabucasin significantly inhibited tumor growth in paclitaxel-resistant TNBC xenograft models and reduced the expression of proliferation marker Ki67 and phosphorylation of STAT3. These findings demonstrate that napabucasin effectively targets paclitaxel-resistant TNBC cells by impairing mitochondrial function and inhibiting key signaling pathways, providing a strong rationale for its further clinical investigation as a therapeutic agent to overcome chemoresistance in TBNC.