BI2536 / Boehringer Ingelheim - LARVOL DELTA

Preclinical Evaluation of Combined Polo-like Kinase 1 Inhibition and Navitoclax in Experimental Models of Lung Cancer. (PubMed, Int J Mol Sci) - "Using Lewis lung carcinoma (LLC1) cells, we evaluated the effects of BI2536 (a PLK-1 inhibitor) and Navitoclax, alone or in combination, in vitro and in male C57BL/6J mice using three lung cancer models: subcutaneous, intranasal, and intrapulmonary. Together, these findings indicate that while PLK-1 inhibition exerts antitumor effects in certain in vivo contexts, the therapeutic synergy observed in vitro with Navitoclax does not consistently translate to in vivo lung cancer models. This study highlights the challenges of translating combinatorial mitotic and apoptotic targeting strategies into effective in vivo therapies and underscores the importance of model selection and tumor microenvironment in preclinical drug evaluation."

Journal • Preclinical • Lung Cancer • Oncology • Solid Tumor • PLK1

Design of Quinazoline Dual Inhibitors Targeting Focal Adhesion Kinase and Polo-like Kinase 1 for Metastatic Cancers: QSAR, Pharmacophore Modelling, and Molecular Docking Approaches. (PubMed, Curr Pharm Des) - "This integrated computational approach combining QSAR modeling, pharmacophore analysis, ADMET prediction, and molecular docking identified promising quinazoline scaffolds as potential dual FAK-PLK1 inhibitors for the treatment of metastatic cancers, such as breast, colon, and non-small cell lung cancer."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PLK1

A prognostic signature based on methionine metabolism-related genes for cervical cancer: integrated transcriptomic and experimental validation. (PubMed, PeerJ) - "Notably, agents such as Cediranib and BI-2536 exhibited markedly lower IC50 values in the high-risk cohort, suggesting their potential efficacy for advanced-stage treatment. qRT-PCR preliminarily indicated the overexpression of four genes in CC tissues within a small clinical cohort. This study establishes a novel MM-based prognostic model for CC and based on in-silico predictions suggests potential therapeutic targets through comprehensive transcriptomic and experimental validation."

Biomarker • Journal • Cervical Cancer • Oncology • Solid Tumor • DNMT3B • SMYD2

Molecular subtyping and therapeutic drug prediction in esophageal squamous cell carcinoma based on manganese-metabolism-related genes. (PubMed, Arab J Gastroenterol) - "MMRG-based subtyping and the reliable prognostic risk score model provide novel insights for predicting prognosis and developing personalized therapy in ESCC."

IO biomarker • Journal • Esophageal Squamous Cell Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • PD-1 • SLC40A1 • TIGIT

Integrative analysis of bulk and single-cell RNA sequencing reveals PHLDA3 as a key regulator of Hypoxic TAMs and prognostic biomarker in HNSC. (PubMed, Discov Oncol) - "PHLDA3 serves as a robust prognostic biomarker for HNSC. Its elevated expression is indicative not only of a low TMB status but also of a critical association with metabolically reprogrammed SPP1+ TAM subpopulations. By potentially sustaining the survival and function of these specific TAMs under hypoxic conditions, PHLDA3 drives the formation of an immunosuppressive microenvironment, highlighting a promising therapeutic target for combined metabolic-immune strategies in HNSC."

Biomarker • IO biomarker • Journal • Tumor mutational burden • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD74 • SPP1 • TMB

Development and Validation of a Prognostic Model for Cervical Cancer Based on Chlamydia trachomatis-Associated Transcriptional Signatures. (PubMed, Int J Womens Health) - "Drug sensitivity analysis identified BI-2536, SB505124, and Sepantronium bromide as potential therapeutic agents for high-risk patients. We established a novel prognostic model for CESC based on CT-related genes in an HPV-positive CESC background, which provides new insights into CT infection-associated immune regulation in CESC and individualized immunotherapy and targeted treatment strategies."

IO biomarker • Journal • Cervical Adenocarcinoma • Cervical Cancer • Cervical Squamous Cell Carcinoma • Infectious Disease • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD4

Design and Synthesis of a Novel Covalent Dihydropteridinone Derivative as a Highly Potent and Orally Bioavailable PLK1 Inhibitor for the Treatment of Chronic Myeloid Leukemia. (PubMed, J Med Chem) - "B9 exhibited low nanomolar enzymatic inhibition and exceptional cellular potency (IC50 = 0.4 nM in K562 leukemia cells), representing a >150-fold improvement over the reversible reference compound BI2536 (61 nM)...In an orthotopic K562 leukemia xenograft model, oral administration of B9 significantly suppressed the bioluminescence of leukemia burden and extended survival rates to 100% over 42 days without observable toxicity. These findings underscore the potential of B9 as a safe, orally bioavailable, and highly potent PLK1 inhibitor for preclinical development."

Journal • Chronic Myeloid Leukemia • Hematological Malignancies • Leukemia • Oncology • PLK1

Global landscape of protein-coding and long non-coding RNA alternative splicing and regulation in the human esophageal squamous cell carcinoma. (PubMed, Cancer Cell Int) - "Our research globally summarized the dysregulation of AS and SF, their associated biological effects, and recommended combined drug treatment strategies for ESCC. This study improves our knowledge of the molecular features of ESCC, supports the development of innovative therapies, and further advances fundamental research on precision medicine for ESCC."

Journal • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma

Biomimetic fusion nanosystem from ginger exosomes and tumor cell membranes: boosting PLK1-targeted therapy in BRCA-heterogeneous HGSOC. (PubMed, J Nanobiotechnology) - "Importantly, synchronizing Bi2536 administration with the circadian peaks of PLK1 expression further augmented its therapeutic efficacy. In summary, our work establishes that the combination of Bi2536 with a biomimetic nano-delivery system, together with its chronotherapeutic administration, constitutes a highly promising and multifaceted strategy for the treatment of HGSOC."

Heterogeneity • Journal • High Grade Serous Ovarian Cancer • Oncology • Ovarian Cancer • Solid Tumor • BRCA • CDK1 • PLK1

Development and validation of a novel prognostic and for osteosarcoma patients utilizing multiple organelle related genes. (PubMed, Discov Oncol) - "Drug sensitivity analysis revealed differential responses to 4 drugs between the risk groups, with the 3 ORGs (ACSS2, CLTCL1 and PLD3) showing positive correlations with 2 drugs (BI_2536, Dactinomycin). Additionally, functional experiments confirmed the role of ACSS2 in OS cell behavior. This novel ORG signature not only provides a valuable tool for patient stratification but also offers insights into the biological processes driving OS progression and potential therapeutic targets."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • ACSS2 • CLTCL1

Construction of a Breast Cancer Predictive Nomogram Based on Diverse Cell Death Methods and Reveal Tumor Microenvironment Characterization. (PubMed, J Biochem Mol Toxicol) - "Patients in the high‑risk group showed improved responses to lapatinib, BI‑2536, OSI‑027, and SB505124, whereas those in the low‑risk subgroup had better sensitivity to axitinib, epirubicin, fulvestrant, and olaparib. Additionally, CD24 overexpression in BC cell lines promoted proliferation and migration, and inhibited apoptosis. These findings contribute to personalized treatment strategies and help elucidate the tumor microenvironment characteristics of BC patients."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • AIF1 • BCL2A1 • CD24 • CREB3L1 • CRIP1 • NKX3-1 • SFRP1 • XBP1

All Screens Lead to Polo-like kinase 1: A Central Node in Cancer Therapeutics and Resistance. (PubMed, Pharmacol Res) - "Emerging evidence supports synergistic potential of new-generation PLK1 inhibitors, such as Onvansertib, with chemo- and immune-therapies. This mini-review and perspective present current insights on PLK1 overexpression and its mechanistic impact on cancer aggressiveness and therapy resistance. We highlight the need for refined patient stratification and innovative combination regimens to exploit PLK1 inhibition in cancer treatment."

Journal • Review • Oncology • PLK1

Leveraging mitochondrial dynamics-related risk signatures to predict the prognosis and tumor microenvironment of lung adenocarcinoma. (PubMed, Discov Oncol) - "This work set up a prognostic model for LUAD based on 8 MDRGs, pinpointing promising biomarkers and targets for LUAD treatment."

Biomarker • Journal • Tumor mutational burden • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CYP27A1 • HMGA2 • SLC2A3 • TMB

Probing monomer - dimer and conformational transitions of PLK1 using catalytic and polo-box domain inhibitors (AACR 2024) - "In this format, we observe heat-induced destabilization of PLK1 upon nanomolar engagement by two lead KD inhibitors, BI2536 and onvansertib, currently being clinically evaluated. These observations have implications for the development of ATP-competitive PLK1 inhibitors because catalytic inhibitors may conversely promote PLK1 non-catalytic functions, which may explain their lack of clinical efficacy to date. Furthermore, the demonstration that the abbapolins are mechanistically unique in terms of blocking the dimerization of PLK through the PBD provides impetus for their development as next generation PLK1 inhibitors."

Oncology • PLK1

The efferocytosis-related genes of SLC26A6, TYRO3, and PDK4 have been identified as predictors of prognosis in hepatocellular carcinoma and are associated with the immune status. (PubMed, Int J Med Sci) - "There were 61 drugs with significant differences in IC50 between the high and low risk groups, such as BI.2536 and PD-173074...We identified three prognostic genes associated with efferocytosis in HCC and integrated them into a risk prognostic model. These genes not only serve as signatures for predicting HCC prognosis but also offer insights into the treatment of HCC."

Biomarker • IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • CD4 • MIR203A • NUTM2A • PDK4

ASXL3 is a potential biomarker of response of SCLC to targeted therapies (AACR 2024) - "Following exposures to 1mM hydroxyurea (HU) for 4, 8, and 24 hours, ATM autophosphorylation levels in ASXL3high SCLC cells were much lower than in ASXL3low SCLC cells...Importantly, low dose HU reduced the IC50 values of the PLK1 inhibitors, BI2536 or NMS-P937 by 80-100-fold in ASXL3high but not ASXL3low SCLC cells, suggesting a strong synergy between these two drugs in ASXL3high SCLC cells. Collectively, these findings suggest that ASXL3 functions to protect cells from lethality induced by genomic instability through monitoring ATM activation. Experiments are underway using SCLC PDX models to demonstrate the efficacy of this combined treatment in-vivo as a prelude to possible evaluation of this drug combination in SCLC patients."

Biomarker • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • ASXL1 • CHEK2 • NEUROD1 • POU2F3 • YAP1

Integrated single-cell and spatial mapping coupled with machine learning unveils core stemness landscapes and regulatory drivers in triple-negative breast cancer. (PubMed, Discov Oncol) - "Our predictive model offers a novel perspective on the stemness landscape of TNBC. These core genes play key roles in maintaining stemness and also serve as potential molecular targets for personalized therapies aimed at TNBC stem-like cells."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANP32B • NOTCH1

Integrating bulk and single cell RNA sequencing to predict the potential therapeutic efficacy of DLX5 in hypopharyngeal squamous cell carcinoma. (PubMed, Eur J Med Res) - "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."

Journal • Head and Neck Cancer • Hypopharyngeal Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD4 • CD8 • DLX5 • TP63

Synergistic Anticancer Effects of the PLK1 Inhibitor BI-2536 and β-Glucan in Colon and Gastric Cancer Cells. (PubMed, Anticancer Res) - "BI-2536 in combination with β-glucan exhibits synergistic anticancer effects in vitro, suggesting a promising strategy for treating colon and gastric cancers."

Journal • Colon Cancer • Colorectal Cancer • Gastric Cancer • Oncology • Solid Tumor • PLK1

Artificial Intelligence Driven Virtual Screening and Molecular Docking Approaches Identified LIFR, BTG2, EPHX2, and PAK3 as Targets and BI-2536, AP-24534, and AZ-628 as Repurposed Drugs for PDAC. (PubMed, IEEE Trans Comput Biol Bioinform) - "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."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BTG2 • LIFR

Plasma proteome mendelian randomization and network pharmacology reveal therapeutic targets for thyroid disorders. (PubMed, Mol Cell Endocrinol) - "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."

Journal • Endocrine Disorders • Oncology • Solid Tumor • Thyroid Gland Carcinoma • CDH1 • FGF19 • RPS6KA6

Copper modulates cell fate through the PLK1-FOXO3a-β-catenin signaling pathway by differentially regulating cuproptosis and EMT. (PubMed, Apoptosis) - "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."

Journal • Colorectal Cancer • Metabolic Disorders • Oncology • Solid Tumor • DLAT • FOXO3 • ITK • PLK1

Design, synthesis and biological activity evaluation of a novel selective inhibitor in PLK1 with acyl or sulfonyl substituted dihydroindole structure. (PubMed, Bioorg Chem) - "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."

Journal • Oncology • PLK1

Construction and validation of a lung adenocarcinoma prognostic model based on neutrophil extracellular traps and oxidative stress-related genes. (PubMed, Eur J Med Res) - "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."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ARHGEF3 • CD79A • CD8 • CLEC7A • EPHB2

Polo-like kinase 1 regulates growth in juvenile Fasciola hepatica. (PubMed, PLoS Pathog) - "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."

Journal • Oncology • PLK1