BI2536 / Boehringer Ingelheim - LARVOL DELTA

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

Multi-omics analysis of the HMGB2+ tumor epithelial cells in lactylation subgroups in colorectal cancer. (PubMed, Cell Biosci) - "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."

Journal • Colorectal Cancer • Oncology • Solid Tumor • HMGB2 • NFYB

Integrated multi-omics analyses identified the H3K18la-based spatiotemporal characteristics and risk-stratified treatment strategy in lung adenocarcinoma. (PubMed, Cancer Lett) - "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."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PLK1

BI-2536 attenuates IPF progression by inhibiting the PLK2/JNK/SP1 Signaling pathway in AT2 cells. (PubMed, Int Immunopharmacol) - "In an in vivo model, BI-2536 significantly ameliorated bleomycin (BLM)-induced pulmonary function decline in IPF mice while suppressing pulmonary inflammation and fibrosis markers, thereby mitigating pathological lung tissue damage. Mechanistically, BI-2536 binds to PLK2, inhibiting downstream phosphorylation of JNK1/2 and SP1, consequently suppressing BLM-induced epithelial-mesenchymal transition (EMT) and fibrotic progression in AT2 cells. In summary, this study demonstrates that BI-2536 delays IPF progression by inhibiting the PLK2/JNK/SP1 signaling pathway in AT2 cells, providing a novel therapeutic agent and target for pulmonary fibrosis treatment."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Pneumonia • Pulmonary Disease • Respiratory Diseases • MAPK8 • PLK2

The effect of PARP and PLK1 dual inhibition on the expression of important protein signaling pathways, DNA damage, and molecular docking scores against MCF-7 and MDA-MB-231 breast cancer cell lines. (PubMed, Ir J Med Sci) - "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."

Journal • Preclinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • BRCA2 • CCND1 • CDKN1A • HER-2 • PLK1 • TP53

Molecular characterization of macrophage-related prognostic factors in glioblastoma revealed by combined analysis on single-cell and bulk transcriptome data. (PubMed, Discov Oncol) - "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."

Biomarker • IO biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • CTLA4 • G0S2 • PD-1 • PD-L1 • TGM2 • TIGIT

PLK1 INHIBITION OFFERS A CLINICALLY RELEVANT STRATEGY FOR DIPG WITH TP53-DEPENDENT THERAPEUTIC SYNERGY (SIOP 2025) - "We evaluated the efficacy of PLK1 inhibition using BI-2536, volasertib, and onvansertib in patient-derived DIPG models, with a focus on TP53 status, pharmacokinetics, and synergy with RT...Co-treatment with vinorelbine significantly increased volasertib CNS accumulation to ~57 nM (p=0.0021), potentiating a combinatorial therapeutic strategy... PLK1 inhibition shows strong anti-tumour activity in DIPG and synergises with RT in TP53-deficient models. These findings support biomarker-guided PLK1-targeted strategies and highlight the need to optimise CNS delivery for clinical translation."

Clinical • Brain Cancer • Diffuse Intrinsic Pontine Glioma • Glioma • Pediatrics • Solid Tumor • PLK1 • TP53

Stemness- and hypoxia-based prognostic stratification index reveals G6PD as a regulator of hypoxia-driven stemness in hepatocellular carcinoma. (PubMed, Front Immunol) - "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."

Biomarker • IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor • Transplantation • HIF1A

PLK1 inhibition enhances gemcitabine-induced apoptosis through PLK1-dependent ERK1/2-Bim and AKT1/Noxa signals in pancreatic cancer cells. (PubMed, Med Oncol) - "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..."

Journal • Oncology • Pancreatic Cancer • Solid Tumor • Transplantation • AKT1 • PMAIP1

Development of Mid-size Bivalent Inhibitors Targeting a Cancer-related Kinase (PubMed, Yakugaku Zasshi) - "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."

Journal • Review • Oncology • PLK1

Exploratory Analysis of Regulated Cell Death-Related Genes as Potential Prognostic Biomarkers in Endometrial Carcinoma. (PubMed, Biomedicines) - "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."

Biomarker • IO biomarker • Journal • Endometrial Cancer • Oncology • Solid Tumor • CD8 • GBP2 • SLC11A1 • TIGIT

Overexpression of PLK1 promotes autophagy-mediated resistance to TMZ in glioblastoma cells by activating NPM1. (PubMed, Biochem Biophys Res Commun) - "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."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • NPM1 • PLK1

Construction of a prognostic model for hepatocellular carcinoma based on necrosis by sodium overload-related genes and identification of ANKRD13B as a new prognostic marker. (PubMed, Funct Integr Genomics) - "Drug sensitivity analysis identified eight chemotherapeutic agents with heightened sensitivity in high-risk patients: BI.2536, Bleomycin, Cisplatin, Doxorubicin, Epothilone B, Gemcitabine, Mitomycin C, and Paclitaxel. We established a novel NECSO prognostic model demonstrating good predictive capacity for HCC prognosis and therapeutic responsiveness. This model helps with personalized clinical management."

Biomarker • IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Panoramic view of MDH1: driving cancer progression and shaping the tumor immune microenvironment. (PubMed, Front Immunol) - "To investigate the role of MDH1 in LUAD cells, a potential inhibitor of MDH1 was identified, BI-2536, and has been confirmed to impact MDH1 activity and impede the growth of LUAD cells. Our findings indicate that MDH1 may serve as a potential prognostic marker and a promising target for cancer immunotherapy."

Biomarker • IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Identification of putative prognostic genes associated with neddylation in prostate cancer (UAA 2025) - "Notably, AP.24534 and Nilotinib showed poorer responses in the high-risk group, while A.443654 and BI.2536 had better responses. This study developed a prognostic model for PRAD that effectively distinguishes between high- and low-risk patients, providing important guidance for the clinical management of prostate cancer. GSVA, immunoscape and drug sensitivity based on high and low risk groups. Single-cell analysis."

Basal Cell Carcinoma • Genito-urinary Cancer • Non-melanoma Skin Cancer • Oncology • Prostate Cancer • Solid Tumor • CD4 • GRIN2B

Machine learning-based characterization of a PANoptosis-associated model for enhancing prognosis and immunotherapy response in lung adenocarcinoma patients. (PubMed, Discov Oncol) - "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."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TRPA1

IGF2BP3 as a Novel Prognostic Biomarker and Therapeutic Target in Lung Adenocarcinoma. (PubMed, Cells) - "Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (-7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine."

Biomarker • IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CD4 • IGF2BP3

Development of a relapse-related RiskScore model to predict the drug sensitivity and prognosis for patients with ovarian cancer. (PubMed, PeerJ) - "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."

Journal • Oncology • Ovarian Cancer • Solid Tumor • KRT19 • LDHA • NOP58 • RPS23

Comprehensive analysis identifies AMIGO2 as a potential prognosis biomarker of pancreatic adenocarcinoma. (PubMed, J Gastrointest Oncol) - "PAAD patients with high AMIGO2 expression were more sensitive to BRD4 inhibitor BI-2536. The growth of PAAD cells was found to be inhibited upon knockdown of AMIGO2. AMIGO2 was identified as prognostic factor in PAAD, suggesting its potential as a biomarker and therapeutic target for PAAD patients."

Biomarker • Journal • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • AMIGO2 • BRD4 • KRAS

Prognostic significance of angiogenesis-associated molecules and Immunologic characteristic in elderly patients with acute myeloid leukemia. (PubMed, Ann Hematol) - "We have constructed an angiogenesis-related gene prognostic signature that enriches the prognostic assessment system for AML and provides novel therapeutic directions for this disease."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • EGLN1 • FKBP5 • FOXP1

Consensus artificial intelligence-driven prognostic signature for predicting the prognosis of hepatocellular carcinoma: a multi-center and large-scale study. (PubMed, NPJ Precis Oncol) - "Collectively, CAIPS serves as a robust multi-dimensional biomarker system for risk stratification, therapy optimization, and personalized HCC management. The concurrent identification of Irinotecan and BI-2536 as targeted agents and PITX1-mediated pathway regulation establishes actionable frameworks for precision oncology."

IO biomarker • Journal • Hepatocellular Cancer • Oncology • Solid Tumor

Genome-wide CRISPR Screening in Embryonic Stem Cells Identifies Synthetic Lethality Interactions in MLH1 and TP53 Deficient Tumors (EACR 2025) - "We further validated the effects of SR1848 (which inhibits NR5A2), ON1231320 or BI2536 (which inhibit PLK2), and blebbistatin (which inhibits MYH10) in cancer cell lines with and without LoF mutations in MLH1 or TP53. Overall, our findings show the potential of genetic screening in haploid hESCs in identifying selective inhibitors and therefore advancing the realm of cancer precision medicine."

Synthetic lethality • Oncology • Solid Tumor • MLH1 • NR5A2 • PLK2 • TP53

Overexpression of oncogenic polo-like kinase 1 disrupts the invasiveness, cell cycle, and apoptosis in synovial sarcoma. (PubMed, J Transl Med) - "PLK1 overexpression was closely associated with poor prognosis. Suppressing PLK1 expression significantly inhibited the growth, invasion, and migration of SS cells, promoted apoptosis, and blocked the G2/M phase of the cell cycle."

Journal • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • BAX • PLK1 • SSX1

Achieving dual-target fluorescent probes for tracing and inhibiting BRD4/PLK1 in tumor cells and tissues synchronously. (PubMed, Eur J Med Chem) - "By inhibiting PLK1 and BRD4, L1 took on obvious tumor cell suppressive activity that was similar to its pharmacophore BI-2536. Furthermore, the mechanism study revealed that dual inhibition of BRD4 and PLK1 modulated the key genes involving the cell cycle and apoptosis pathways, overcoming compensatory effects compared with the single-target inhibitors. Our work would provide a reliable toolkit for the development of PLK1/BRD4 dual-target inhibitors for cancer diagnostic and therapeutic agents, and bring out the ideas and cases for the design of visualization and therapy dual functional probes."

Journal • Oncology • BRD4 • PLK1

Identification of Ion Channel-Associated Prognostic Biomarkers for Lung Adenocarcinoma. (PubMed, J Environ Pathol Toxicol Oncol) - "The drug prediction results showed that individuals with LUAD in the low-risk group were more sensitive to paclitaxel, BI 2536, pyrimethamine, and VX-680, while individuals with LUAD in the high-risk group to erlotinib, sorafenib, panitumumab, PHA-665752, and roscovitine. In summary, ion channel-related genes can provide valuable information for prognosis assessment and drug treatment of LUAD patients."

Biomarker • IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor