BI2536

Through bioinformatics analysis, it was discovered that DLX5 exerts an oncogenic role in HPSCC through co-amplification with TP63 and activation of the MAPK signaling pathway, with functional assays further confirming its promotion of malignant phenotypes. High expression of DLX5 correlates positively with immunosuppressive cells, such as M2 macrophages, and negatively with antitumor CD8+ T cells, indicating an association with an immunosuppressive microenvironment. These findings highlight DLX5 as a key determinant of poor prognosis in HPSCC.

BI-2536 in combination with β-glucan exhibits synergistic anticancer effects in vitro, suggesting a promising strategy for treating colon and gastric cancers.

By synergizing genetic epidemiology with network pharmacology, this study delineates shared genetic architecture among thyroid disorders and nominates seven high-confidence targets with therapeutic potential. The integrative framework advances precision medicine by bridging causal plasma protein identification, mechanistic pathway mapping, and drug repurposing, offering a blueprint for multi-omics-driven drug discovery in endocrine pathologies.

The pharmacokinetics study strengthened our results that the identified drugs can be used as a therapeutic for PDAC as they obey Lipinski's rule. In conclusion, identified genes can act as prognostic markers, and drugs could be used as potential therapeutics for PDAC.

In contrast, co-treatment with Cu and copper ionophore elesclomol (Cu-ES) triggered cuproptosis, a unique copper-dependent form of cell death, accompanied by mitochondrial dysfunction, dihydrolipoamide S-acetyltransferase aggregation, and ATP depletion. The PLK1 inhibitor BI-2536 recapitulated the effects of Cu-ES and exhibited synergistic activity when combined with Cu-ES, enhancing both cell death and EMT suppression. These findings highlight a novel regulatory mechanism of EMT through copper signaling and support copper-based combination therapies as a promising approach to simultaneously inhibit tumor growth and metastasis in colorectal cancer.

The pharmacokinetic profile of B7 in rats is also superior to that of BI 2536 (AUC0-t = 578 ng·h·mL-1 vs 283 ng·h·mL-1), and the bioavailability of B7 is 20.1 %, and no apparent toxicity was observed in the acute toxicity assay (20 mg/kg). These results suggest that B7 is a promising PLK1 inhibitor.

The constructed prognostic model by NETs and oxidative stress-relevant genes effectively predicts LUAD prognosis, correlates with immune microenvironment characteristics, and guides drug sensitivity, providing novel insights for LUAD prognostic assessment and personalized therapy.

A PLK inhibitor (BI 2536) was shown to phenocopy the fhplk1-RNAi phenotype in a dose-dependent manner, supporting the feasibility of targeting F. hepatica neoblast-like cells through kinase inhibitors...While many neurotransmitter pathways promote proliferation in mammalian systems the interaction between neoblast-like stem cells and neuronal signalling in parasitic flatworms remains elusive. Here, the transcriptomic response of fhplk1-RNAi juveniles supports a link between neoblast-like stem cell driven growth/development and neuronal signalling.

In-silico drug screening suggests that targeting Polo-like kinase 1 (PLK1) with BI-2536 could be an effective strategy for high-risk LUAD patients. This study offers a deeper understanding of LUAD metabolism and immune evasion at single-cell and spatial resolution, proposing potential therapeutic targets and a risk-stratified treatment strategy for precision medicine.

In summary, HMGB2+Epi represents a key lactylation-enriched subgroup, with the NFYB-HMGB2 axis driving CRC progression via lactylation. BI-2536 as a tool compound implicating the HMGB2-lactylation axis, and the HMGB2+Epi-based risk model provides a novel target for precision CRC therapy.

The increased expression of PLK1, p53, p21, γH2AX, Nrf-2, cyclin E, A, and B1, along with the decreased expression of HER-2, NF-κB, and cyclin D1 in breast cancer cells, suggests that PLK1 inhibition can enhance the efficacy of PARP inhibitors.

This study reveals the molecular characteristics of key prognostic factors in GBM, highlighting the importance of immune cell abundance and drug sensitivity in glioma treatment, and provides potential biomarkers and therapeutic targets for future clinical research and treatment strategies.