BI2536

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.

This study provides further insights into stemness-hypoxia interaction in HCC and delivers a clinically applicable predictive tool for prognosis. BI2536's synergy potential and the therapeutic value of G6PD targeting in stemness regulation advance individualized therapeutic strategies for HCC.

We detected the expression of PLK1 in pancreatic cancer tissues and cell lines and study the effects of PLK1 and Gemcitabine on cell viability and apoptosis of GEM-resistant pancreatic cancer PANC-1 cells and Gemcitabine sensitive BxPC-3 cells; Using inhibitors or siRNA, we further investigate the effects of PLK1 on ERK1/2, AKT1, and pro-apoptotic genes PUMA, Bim, and Noxa; We finally investigated the effect of the combined onvansertib and Gemcitabine on the growth of PANC-1 subcutaneous transplant tumors in nude mice and explored its possible mechanism of action...BI2536 (a PLK1 kinase inhibitor) treatment recures the Gemcitabine sensitivity in the PLK -transfected BxPC-3 cells by upregulation of Bim and Noxa expression in vitro...Targeting PLK1 sensitizes PDAC cells to gemcitabine in vitro and in vivo. This indicates that combination therapy with PLK1 inhibitor may overcome gemcitabine resistance, offering a promising new therapeutic option for the treatment of gemcitabine-resistant human pancreatic cancer.

Here, I developed bivalent Plk1 inhibitors, in which the PBD-binding peptides are conjugated with the known KD-binding inhibitors BI2536 or wortmannin using PEG linkers. These bivalent inhibitors exhibit up to 100-fold enhanced Plk1 affinity relative to the best monovalent PBD-binding ligands, higher selectivity for tested kinases compared to BI2536, and significant cytotoxicity against HeLa cells.

Based on sensitivity analysis of chemotherapeutic agents, we found the highest positive correlation between SLC11A1 and "BI.2536" and the strongest passive correlation of HCLS1 and GBP2 with "Ribociclib", as well as P2RX7 with "BMS.754807". Quantitative real-time polymerase chain reaction suggested that the expression trends of GBP2, P2RX7, and HCLS1 were consistent with the results of bioinformatic analysis. Regulated cell death-related genes (GBP2, SLC11A1, P2RX7, and HCLS1) may play a role in endometrial carcinoma development, which can provide new ideas for the treatment and prognosis prediction of this disease.

PLK1 inhibition effectively suppresses autophagy, cell proliferation, TMZ resistance, and tumorigenicity, while promoting apoptosis in GBM cells through the regulation of NPM1 serine 4 phosphorylation. Targeting PLK1 presents a promising therapeutic strategy for the treatment of GBM.

The present study developed a PRS using 101 machine learning combination algorithms, which could aid in risk stratification and prognosis for LUAD patients. The candidate drugs and target may provide new insights in the treatment of high PRS group patients.

Further, six drugs (Vinorelbine, GW-2580, S-Trityl-L-cysteine, BI-2536, CP466722, NSC-87877) were found to be correlated with the RiskScore. In addition, KRT19 silencing markedly inhibited the invasion and migration of OC cells. This study established a relapse-related RiskScore model based on five prognostic genes (LDHA, NOP58, NMU, KRT19, and RPS23), offering novel insights into the recurrence mechanisms in OC and contributing to the development of individualized treatment strategies.