napabucasin (BBI608)

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.

We used four stemness inhibitors-salinomycin, SB-431542, JIB-04, and napabucasin-each targeting different pathways (Wnt/β-catenin, TGF-β, histone demethylation, and STAT3, respectively), to evaluate their effects on CMS4 CRC cell lines (HCT116 and SW620) and human peripheral blood-derived macrophages in an indirect co-culture model. Our study highlights the dual potential of stemness inhibitors to target both cancer cells and the immune microenvironment. These findings offer promising strategies for enhancing favorable immunomodulation in mesenchymal-like colorectal tumors.

This study is the first to show that FC restrains the EMT of TNBC cells by obstructing the STAT3 pathway and hinders the M2 polarization of macrophages and immune evasion. Therefore, FC holds the possibility of being utilized as a therapeutic remedy for TNBC.

Cotreatment with celecoxib effectively diminished these changes induced by PGE2...STAT3 inhibitor napabucasin also inhibited COX-2 expression both in the presence and absence of IFN-γ...HH044 treatment also significantly reduced tumor PGE2 levels in vivo. Our study demonstrates the positive feedback loop linking nNOS-mediated NO signaling to the COX-2/PGE2 signaling axis in melanoma, which further potentiates the pro-tumorigenic activity of IFN-γ.

A high-throughput screening of a pharmacological library with 423 compounds revealed that napabucasin, a signal transducer and activator of transcription 3 (STAT3) inhibitor, synergistically potentiated the growth inhibition effect of the KRASG12C inhibitor sotorasib in sensitive and resistant KRASG12C NSCLC cell lines. Moreover, we unveiled and verified the binding site of phosphorylated STAT3 at the HLA-B promoter, an inhibitor ligand for NK cells. Our study dissected an unknown mechanism of adaptive resistance to KRASG12C inhibitors, with the STAT3 activation sustaining the regrowth of tumor cells under KRAS inhibition and up-regulating HLA-B transcription to dampen the cytotoxicity of infiltrated NK cells.

The anti-proliferative activity evaluation revealed that most of these compounds exhibited superior inhibitory activity against MDA-MB-231 and MDA-MB-468 breast cancer cell lines compared to napabucasin...Meanwhile, 16c showed encouraging anti-tumor efficacy in the MDA-MB-231 xenograft model. In summary, this protocol provides a new vision and new chemical entity for dual targeting STAT3 and NQO1.