ZM 447439 / Bio-Techne - LARVOL DELTA

The Aurora B inhibitor ZM-447439 induces caspase-independent necrosis-like death in v-Src oncogene-expressing cells via accumulation of extra-lysosomal cathepsin B. (PubMed, Exp Cell Res) - "Treatment with the cathepsin B inhibitor CA-074 methyl ester mitigates cell death, similar to the pan-cysteine cathepsin inhibitor E64d treatment. These results suggest that the Aurora B inhibitor ZM-447439 potentiates caspase-independent necrosis-like death in v-Src-expressing cells partly through the accumulation of extra-lysosomal cathepsin B. The Aurora B inhibitors might be promising therapeutic agents for Src-driven cancers."

Journal • Oncology • CTSB

DRUG SENSITIVITY AND CLINICAL APPLICATIONS BASED ON CUPROPTOSIS-ASSOCIATED LNCRNA PROGNOSTIC IMPACT IN ACUTE MYELOID LEUKEMIA (EBMT 2025) - "Furthermore, patients in the high-risk group were less sensitive to chemotherapies such as Axitinib, GSK429286A, Navitoclax, and ZM-447439, suggesting that the administration of drugs for this type of patients may be less effective with higher toxicity, so optimized therapeutic strategies are necessary for them. This study provided new perspectives for the personalized treatment and precision therapy of AML, enhancing the foundation for the development of targeted therapy based on lncRNA. Clinical Trial Registry: None."

Clinical • Acute Myelogenous Leukemia • Gene Therapies • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Structural characterization of Aurora kinase B modulation by Epigallocatechin gallate: Insights from docking and dynamics simulations. (PubMed, J Mol Graph Model) - "Synthetic inhibitors like AZD1152 and ZM447439 show selectivity for AURKB but often lack specificity due to high homology within the aurora kinase family. The study also noted transitions in the overall protein secondary structures, such as turn to coil, coil to sheet, and coil to helix, contributing to a stable structure upon EGCG binding. These findings highlight the complex interplay between EGCG and AURKB, providing insights into the conformational dynamics and structural alterations induced by this interaction, which has implications for reducing glioma cell chemosensitivity to therapeutic drugs."

Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • AURKB • EGFR

Stem cell status and prognostic applications of cuproptosis-associated lncRNAs in acute myeloid leukemia. (PubMed, Front Cell Dev Biol) - "High-risk patients demonstrated lower sensitivity to chemotherapeutic agents such as Axitinib, GSK429286A, Navitoclax, and ZM-447439, underscoring the need for alternative therapeutic strategies. CRLPM offers a promising framework for integrating stem cell-focused approaches into personalized treatment regimens, paving the way for precision medicine in AML management."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Construction of a novel lipid drop-mitochondria-associated genetic profile for predicting the survival and prognosis of lung adenocarcinoma. (PubMed, Discov Oncol) - "Our results suggest that the LD-M risk score is an effective prognostic indicator for individualized treatment of LUAD."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CAV2 • CYP24A1

The cell death-related genes machine learning model for precise therapy and clinical drug selection in hepatocellular carcinoma. (PubMed, J Cell Mol Med) - "Moreover, our investigation has shown that AZD2014, SB505124, LJI308 and OSI-207 show a greater efficacy in patients in the low-risk category. Conversely, for the high-risk group patients, PD173074, ZM447439 and CZC24832 exhibit a stronger response...This innovative model provides a novel approach for forecasting prognosis and assessing drug sensitivity in HCC patients, driving a more personalized and efficacious treatment paradigm, elevating clinical outcomes. Nonetheless, additional research endeavours are required to confirm the model's precision and assess its potential to inform clinical decision-making for HCC patients."

Journal • Machine learning • Tumor mutational burden • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • TMB

V-Src delocalizes Aurora B by suppressing Aurora B kinase activity during monopolar cytokinesis. (PubMed, Cell Signal) - "Furthermore, like v-Src, treatment with the Aurora B inhibitor ZM447439 also caused Aurora B delocalization at concentrations that partially inhibited Aurora B autophosphorylation. Given that phosphorylation of Aurora B by v-Src was not observed, these results suggest that v-Src causes Aurora B delocalization by indirectly suppressing Aurora B kinase activity."

Journal • Oncology • Sarcoma • Solid Tumor • CDK1 • CSK • SRC

INTEGRATED ATAC-SEQ AND SINGLE-CELL SYNERGISTIC CHEMOSENSITIVITY PROFILING IDENTIFIES RATIONAL DRUG COMBINATIONS IN IBRUTINIB-TREATED CLL PATIENTS (EHA 2018) - P=N/A; "...Recent studies have explored combined use of ibrutinib with inhibitors for the proteasome (carfilzomib), BCL2i (venetoclax), and HDAC (abexinostat) in preclinical models, which has shown promising initial results...Results ATACseqidentified increases in chromatin accessibility and chemosensitivity in proteasome, inflammatory NF-B/TNF signaling, CoA biosynthesis, PI3K/Akt, pathways, along with changes affecting genes such as FOXO3 and IBa, and both the ex vivo drug testing of samples from patients after clinical ibrutinb and ex vivo synergy screeningrevealed that ibrutinib treatment in vivo and in vitro sensitizes CLL cells to compounds such as the proteasome inhibitor bortezomib, the JAK inhibitor ruxolitinib, the bisphosphate zoledronate, and the aurora kinaseinhibitor ZM447439... Our results show that synergistic combination and informatics-integration of chromatin profiling with functional drug screening is a powerful tool to identify targetable path

Clinical • Chronic Lymphocytic Leukemia • Indolent Lymphoma

Identifying the role of transient receptor potential channels (TRPs) in kidney renal clear cell carcinoma and their potential therapeutic significances using genomic and transcriptome analyses. (PubMed, BMC Med Genomics) - "Besides, high-risk KIRC patients might benefit from ABT888, AZD6244, AZD7762, Bosutinib, Camptothecin, CI1040, JNK inhibitor VIII, KU55933, Lenalidomide, Nilotinib, PLX4720, RO3306, Vinblastine, and ZM.447439; however, low-risk populations might benefit from Bicalutamide, FH535, and OSI906. Finally, calibration curves were used to validate the nomogram with a satisfactory predictive survival probability. In conclusion, this research provides useful insight that can aid and guide clinical practice and scientific research."

Journal • Clear Cell Renal Cell Carcinoma • Immune Modulation • Inflammation • Oncology • Renal Cell Carcinoma • Solid Tumor • TMB

Construction and Validation of a Novel Prognostic Signature of Idiopathic Pulmonary Fibrosis by Identifying Subtypes Based on Genes Related to 7-Methylguanosine Modification. (PubMed, Front Genet) - "Three drugs (ZM447439-1050, AZD1332-1463, and Ribociclib-1632) were considered sensitive to patients with high m7GPS risk scores. This study developed a novel m7GPS, which is a reliable indicator for predicting the survival status of IPF patients and is identified as an effective marker for prognosis and screening of IPF patients."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • CCN1

The Prognostic Model and Drug Sensitivity of LKB1-Mutant Lung Adenocarcinoma Based on Immune Landscape. (PubMed, Front Mol Biosci) - "ZM.447439 was an appropriate treatment for the high-risk group of patients. This risk model is only suitable for LKB1-mutant tumors; it performed poorly in LUAD patients with wild-type LKB1. Our findings indicate the potential role of immunity in LKB1-mutant LUAD, providing novel insights into prognosis and guiding effective immunotherapy."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • STK11

Improving Generation of Cardiac Organoids from Human Pluripotent Stem Cells Using the Aurora Kinase Inhibitor ZM447439. (PubMed, Biomedicines) - "We validated their maturity through electro-physiological- and image-based functional assays and gene profiling with next-generation sequencing, and then applied these cells to multi-electrode array platforms to monitor the cardio-toxicity of drugs related to cardiac arrhythmia; the results confirmed the drug reactivity of hCOs. These findings may enable determination of the regulatory mechanism of cell cycles underlying the generation of iPSC-derived hCOs, providing a valuable drug testing platform."

Journal • Atrial Fibrillation • Cardiovascular

Biological and Clinical Significance of PIM1 Genetic Alterations in Diffuse Large B-Cell Lymphoma (ASH 2021) - "We further found that compared to patients with low-risk score, patients with high-risk score had higher sensitivity to some drugs of targeting the immune microenvironment, including TGFβ receptor inhibitors SB525334 ( P <0.0001) and SB505124 ( P <0.0001) and immunomodulator Lenalidomide ( P =0.041), as well as NF-κB inhibitors Parthenolide ( P <0.0001) and TPCA-1 ( P <0.0001) and JAK inhibitors Ruxolitinib ( P =0.014) and TG101348 ( P =0.0053), accompanying with significantly lower IC50 values. In addition, another common chemotherapeutic drug Gemcitabine was also predicted to be more sensitive for patients with high-risk score ( P =0.047). Other targeted drugs such as Aurora kinase inhibitors VX-680 ( P <0.0001) and ZM-447439 ( P =0.014), Bcl-2 inhibitors Obatoclax Mesylate ( P =0.00036) and Navitoclax ( P <0.0001), and CDK inhibitors Roscovitine ( P =0.0012), AT-7519 ( P =0.0033), PHA-793887 ( P <0.0001) and THZ2-49 ( P =0.0053) also exhibited..."

Clinical • IO biomarker • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immune Modulation • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD79B • IL17A • MYD88 • PIM1 • PRDM1 • TGFB1

Advances in targeted therapy for osteosarcoma based on molecular classification. (PubMed, Pharmacol Res) - "Therefore, we indicated the importance of molecular classification on the targeted therapy for osteosarcoma. And the stratification of patients based on the genetic characteristics of osteosarcoma will help to obtain a better therapeutic response to targeted therapies, bringing us closer to the era of personalized medicine."

Journal • Review • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Combination Treatment of OSI-906 with Aurora B Inhibitor Reduces Cell Viability via Cyclin B1 Degradation-Induced Mitotic Slippage. (PubMed, Int J Mol Sci) - "We recently reported that OSI-906, an IGF1R inhibitor, in combination with the Aurora B inhibitor ZM447439 suppresses cell proliferation. The generation of over-replicated cells with massive aneuploidy may be the cause of reduction of cell viability and cell death. This study provides new possibilities of cancer chemotherapy."

Journal • Oncology • CCNB1

Compromised MPS1 Activity Induces Multipolar Spindle Formation in Oocytes From Aged Mares: Establishing the Horse as a Natural Animal Model to Study Age-Induced Oocyte Meiotic Spindle Instability. (PubMed, Front Cell Dev Biol) - "To investigate the importance of MPS1 and AURKC function in spindle (re)assembly, various concentrations of a MPS1 inhibitor (MPS1i, Compound 5) or an AURK inhibitor (AURKi, ZM447439) were included after nocodazole washout...Overall, this suggests that compromised Mps1 activity predisposes to meiotic spindle instability in aged mare oocytes. This spindle instability could predispose to chromosome segregation errors."

Journal • Preclinical • CNS Disorders • Oncology • MPS1

[VIRTUAL] Mitotic inhibitors suppresses tumor formation and metastasis of triple negative breast cancer (TNBC) (AACR 2021) - "Furthermore, we investigated that the mitosis-related small molecule protein kinase inhibitors such as VX-680, ZM447439, BI2536, and apcin also inhibit tumor cell proliferation, migration, and invasion. Cdc20 might serve as a potential marker of disease progression and as a principal potential therapeutic target. Also, mitosis-related protein kinase inhibitors are additional potential therapy to suppress cancer cell progression and invasion in TNBC effectively."

Breast Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Triple Negative Breast Cancer • CDC20

Inhibition of Cdc20 suppresses the metastasis in triple negative breast cancer (TNBC). (PubMed, Breast Cancer) - "These results suggest an essential role of Cdc20 in tumor formation and metastasis of TNBC, which might be a potential target therapy for TNBC treatment."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDC20

Targeting Insulin-Like Growth Factor 1 Receptor Delays M-Phase Progression and Synergizes with Aurora B Inhibition to Suppress Cell Proliferation. (PubMed, Int J Mol Sci) - "Moreover, a similar delay in M phase was observed following 2 h of incubation with the IGF1R inhibitors OSI-906 and NVP-ADW742. Live-cell imaging revealed that both prolonged prometaphase and prolonged metaphase underlie the delay and this can be abrogated by the inhibition of Mps1 with AZ3146, suggesting activation of the Spindle Assembly Checkpoint when IGF1R is inhibited. Furthermore, incubation with the Aurora B inhibitor ZM447439 potentiated the IGF1R inhibitor-induced suppression of cell proliferation, opening up new possibilities for more effective cancer chemotherapy."

Journal • Oncology

Cytogenetically-based biodosimetry after high doses of radiation. (PubMed, PLoS One) - "The assay is modified either through inhibitions of the G2/M and spindle checkpoints with the addition of caffeine and/or ZM447439 (an Aurora kinase inhibitor), respectively to the blood cultures at select times during the assay...When the dose-effect curves were fitted to take into account the turnover phenomenon observed at higher doses, best fitting was achieved when the combination of both inhibitors was used. These techniques permit reliable dose reconstruction after high doses of radiation with a method that can be adapted to high-throughput automated sample processing systems."

Journal

THE ACTIVITY OF AURORA KINASE B IS REQUIRED FOR DENGUE VIRUS RELEASE. (PubMed, Virus Res) - "Moreover, confocal microscopy analysis of DENV-infected ZM 447439-treated cells show a delocalization of viral components from the replicative complexes. In summary, these observations indicate that AurKB participates in DENV viral morphogenesis or release."

Journal • Dengue Fever

Dynamic Phosphorylation of NudC by Aurora B in Cytokinesis. (PubMed) - PLoS One - "In contrast, reconstitution with the T40D phospho-mimetic NudC was inefficient in supporting the completion of cytokinesis. These results suggest that that dynamic phosphorylation of NudC by Aurora B regulates cytokinesis."

Journal • Biosimilar

Antitumor profiles and cardiac electrophysiological effects of aurora kinase inhibitor ZM447439. (PubMed, Korean J Physiol Pharmacol) - "In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity."

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