barasertib (AZD1152) / AstraZeneca - LARVOL DELTA

The current landscape of quinazoline derivatives with in vivo anticancer therapeutic potential-part I. (PubMed, Future Med Chem) - "Moreover, several quinazoline hybrids, exemplified by Fruquintinib (quinazoline-benzofuran hybrid) and Barasertib (quinazoline-pyrazole hybrid), have already been applied in clinics for cancer therapy, indicating that the rational design of quinazoline hybrids may provide valuable chemotherapeutics for cancer therapy. This review outlines the current scenario of the in vivo anticancer therapeutic potential of quinazoline hybrids, together with modes of action, toxicity, and pharmacokinetic properties, developed from 2015 onwards, aiming to provide promising candidates for further preclinical/clinical evaluations and to facilitate further rational design."

Journal • Preclinical • Review • Oncology

Evaluation of the effects of MDM2 inhibitor and epigenetic modifiers in combination with AURKB inhibitors for treating lung cancer (AACR 2025) - "We also examined the anti-cancer effects of RG-7388, SAHA, CM-272, and Barasertib (an AURKB inhibitor), in modulating cell cycle regulation...Our findings confirm that AURKB levels can be down-regulated by using the combination of MDM2 inhibitors and epigenetic regulators such as SAHA and CM-272. However, the therapeutic efficiency of these combinations needs to be verified using in vivo experimental models."

Combination therapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • ALDH1A1 • AURKB • BCL2L1 • CASP7 • CCNA2 • CDC25C • CDK4 • CDK6 • CDKN1A • GNRP • PARP1 • XIAP

Concurrent inhibition of the serine/threonine protein kinase AURKB and the fatty acid oxidation enzyme CPT1A demonstrates synthetic lethality in preclinical glioblastoma models (AACR 2025) - "Remarkably, the selective AURKB inhibitor barasertib was found to potently suppress the growth of established GBM cell lines, patient-derived xenograft models, and neurosphere cultures at low, nanomolar concentrations. Furthermore, the BH3-mimetic ABT263 was found to reduce the growth of GBM lines in the context of AURKB loss of function, likely due to the heightened dependence on mitochondrial metabolism. These findings uncover a previously unappreciated role for AURKB in regulating GBM metabolism and provide a strong rationale for further developing AURKB-targeted therapies, potentially in combination with metabolic inhibitors and BH3-mimetics, to improve clinical outcomes for patients with GBM."

Preclinical • Synthetic lethality • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • AURKB • CPT1A

Common Regulatory Mechanisms Mediated by Cuproptosis Genes in Inflammatory Bowel Disease and Major Depressive Disorder. (PubMed, Genes (Basel)) - "These findings have substantially enhanced our understanding of the similarities and differences in the regulatory mechanisms of CRGs within brain-gut axis diseases. Key biomarkers have been identified, and potential therapeutic drugs have been predicted to effectively target IBD and MDD."

Journal • CNS Disorders • Depression • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Major Depressive Disorder • Mood Disorders • Psychiatry • CDKN2A • DLAT • LIAS • SLC31A1

Co-inhibition of Aurora kinase B and SUV4-20H induces synthetic lethality in Wild-type p53 deficient cancer cells. (PubMed, Mol Cancer Ther) - "Barasertib (AZD2811) targets the mitotic kinase Aurora B (AURKB) and is in current clinical trials for various cancers. Lastly, we found in two different p53 mutated cell line tumor models that barasertib plus A196 has greater anti-tumor activity than either single agent. Our results suggest co-targeting of AURKB and SUV4-20H1/2 could be effective against p53-mutated or deficient cancers, including TNBCs in which approximately 80% of cases are p53 mutated."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AURKB • TP53

Unraveling AURKB as a potential therapeutic target in pulmonary hypertension using integrated transcriptomic analysis and pre-clinical studies. (PubMed, Cell Rep Med) - "Finally, we demonstrate that the combination of barasertib with a p21 attenuator is more effective in reducing vascular remodeling than either drug alone. These findings provide insight into strategies for therapeutic manipulation."

Journal • Preclinical • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • AURKB • CDKN1A

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

Aurora kinase B inhibitor AZD1152: repurposing for treatment of lupus nephritis driven by the results of clinical trials. (PubMed, EBioMedicine) - "This study presents a drug development strategy that integrates clinically validated LN therapies with drug repurposing approaches. This strategy could accelerate drug development and clinical translation processes for LN."

Journal • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Renal Disease • Systemic Lupus Erythematosus • AURKB

Evaluation of ribociclib, abemaciclib and palbociclib resistance in ER+ breast cancer cells reveal novel therapeutic opportunities in ER+/HER2- breast cancers (SABCS 2024) - "CDK4/6i resistant and sensitive cells were evaluated for spheroid forming ability, cell cycle progression, apoptosis, cross resistance to other CDK4/6i, whole genome RNA sequencing, and cisplatin/volasertib (PLK1 inhibitor)/barasertib (Arora kinase B inhibitor) sensitivity. In ER+/ HER2− BCs, pathways to resistance to CDK4/6i therapy are complex and diverse. PLK1 or Aurora Kinase B targeting could be an attractive therapeutic strategy in certain CDK4/6i resistant ER+ BCs."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • AURKB • CDK6 • ER • HER-2 • TGFB1

Targeting the EGFR and Spindle Assembly Checkpoint Pathways in Oral Cancer: A Plausible Alliance to Enhance Cell Death. (PubMed, Cancers (Basel)) - " We analyzed the effects of co-treating OSCC cells with small molecules targeting MPS-1 (BAY1217389), Aurora-B (Barasertib), or KSP (Ispinesib), alongside Cetuximab. Additionally, we examined EGFR, MPS-1, Aurora-B, and KSP expression in OSCC patient samples, revealing their clinicopathologic significance. This combinatorial approach suggests a promising strategy to improve treatment outcomes in OSCC."

Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

Identification of Vesicle-Mediated Transport-Related Genes for Predicting Prognosis, Immunotherapy Response, and Drug Screening in Cervical Cancer. (PubMed, Immun Inflamm Dis) - "The VMTRG-based prognostic model demonstrates reliable clinical prognostic value and enhances understanding of vesicle-mediated transport mechanisms in CC."

Biomarker • IO biomarker • Journal • Cervical Cancer • Oncology • Solid Tumor

AZD1152: Repurposing for Treatment of Lupus Nephritis Driven by the Results of Clinical Trials (KIDNEY WEEK 2024) - "Combination therapy consisting of mycophenolate mofetil ,tacrolimus and glucocorticoid achieved a 20% higher CR than conventional therapy. This is the first study to illustrate the therapeutic effect of AZD1152 in SLE and renal injury. The comparable efficacy of AZD1152 to combination regime means it is able to further reduce the side effects of drug combination. Our study also revealed the potential of AURKB as a biomarker to predict LN disease activity."

Clinical • Chronic Kidney Disease • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • AURKB

Targeting Aurora Kinase B Improves Vascular Remodeling in Pulmonary Arterial Hypertension (AHA 2024) - "Our research identified AURKB as a novel therapeutic target and suggests that combining anti-remodeling drugs with senotherapeutics may be more effective in counteracting vascular remodeling in PAH."

Cardiovascular • Pulmonary Arterial Hypertension • Respiratory Diseases • AURKB • BIRC5 • CDKN1A • FOXM1 • PLK1

Cell cycle inhibitors activate hypoxia-induced DDX41-STING pathway to mediate anti-tumor immune response in liver cancer. (PubMed, JCI Insight) - "We demonstrated that Paclitaxel (microtubule stabilizer), Palbociclib (cyclin dependent kinase 4/6 inhibitor), AZD1152 and GSK1070916 (aurora kinase B inhibitors) have anti-cancer functions beyond arresting cell cycle. We observed a trend that Paclitaxel suppressed STINGWT HCC more effectively than STINGKO HCC, suggesting that STING might contribute to the anti-tumor effects of Paclitaxel. Our study revealed the immune-mediated tumor-suppressing properties of cell cycle inhibitors and suggested combined treatment with immunotherapy as a potential therapeutic approach."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • AURKB • DDX41 • HIF1A • STING

Aurora B and Aurora C pools at two chromosomal regions collaboratively maintain chromosome alignment and prevent aneuploidy at the second meiotic division in mammalian oocytes. (PubMed, Front Cell Dev Biol) - "We found that kinetochore-microtubule attachments at single chromatids were corrected at both prometaphase II and metaphase II stages, but that single chromatids compared to paired chromatids were more prone to misalignments following treatment of oocytes with the Aurora B/C inhibitory drugs AZD1152 and GSK1070916. We conclude that the Aurora B/C pool at the inner central region stabilizes chromosome alignment during metaphase II arrest, while Aurora B/C localized at the kinetochore assist in re-establishing chromosome positioning at the metaphase plate if alignment is lost. Collaboratively these two pools prevent missegregation and aneuploidy at the second meiotic division in mammalian oocytes."

Journal

Aurora kinase B: A New Therapeutic Target in PAH (ERS 2024) - "Finally, the combination of Barasertib with the p21 attenuator UC2288 was more effective in reducing vascular remodeling in Su/Hx rats than either drug alone (EVG). Our research identified AURKB as a novel therapeutic target and suggests that combining anti-remodeling drugs with senotherapeutics may be more effective in counteracting vascular remodeling in PAH."

Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • ANXA5 • AURKB • BIRC5 • CDKN1A • FOXM1 • PLK1

Role of AURKB Inhibition in Reducing Proliferation and Enhancing Effects of Radiotherapy in Triple-Negative Breast Cancer. (PubMed, Breast Cancer (Dove Med Press)) - "The combination of AZD1152 at IC50 concentrations together with ionizing radiation further reduced colony formation as compared to the single agent treatment. Our data support the notion that inhibition of the AURKB pathway is a promising strategy for treatment and radiosensitization of TNBC and warrants further translational studies."

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

Coupling Kinesin Spindle Protein and Aurora B Inhibition with Apoptosis Induction Enhances Oral Cancer Cell Killing. (PubMed, Cancers (Basel)) - "Here, we investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic Navitoclax in oral cancer cells treated with the selective KSP inhibitor, Ispinesib, or AurB inhibitor, Barasertib, aiming to potentiate cell death. A mechanistic analysis underlying this synergistic activity, undertaken by live-cell imaging, is presented. Our data underscore the importance of combining BH3-mimetics with antimitotics in clinical trials to maximize their effectiveness."

Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • AURKB

Aurora Kinases as Novel Targets for the Treatment of Aggressive Meningiomas (EACR 2024) - "Therefore, we investigated the efficacy of AURKAi alisertib, AURKBi barasertib, and the pan-Aurora kinase inhibitor danusertib as potential therapeutics for the treatment of MGMs.Material and Methods RNAi-mediated knockdown experiments were conducted in benign (Ben-Men-1) and anaplastic MGM cell lines (NCH93). Alisertib demonstrated substantial in vivo anti-tumor effects while showing a high tolerability. These novel data suggest that targeting Aurora kinases could offer new therapeutic options for patients with aggressive MGMs in future years."

Brain Cancer • CNS Tumor • Meningioma • Oncology • Solid Tumor • AURKA • AURKB

AURKB promotes colorectal cancer progression by triggering the phosphorylation of histone H3 at serine 10 to activate CCNE1 expression. (PubMed, Aging (Albany NY)) - "Furthermore, it was showed that the inhibitor specific for AURKB (AZD1152) can suppress CCNE1 expression in CRC cells and inhibit tumor cell growth. To conclude, this research demonstrates that AURKB accelerated the tumorigenesis of CRC through its potential to epigenetically activate CCNE1 expression, suggesting AURKB as a promising therapeutic target in CRC."

Epigenetic controller • Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • AURKB • CCNE1

Cell cycle inhibitors exhibit anti-tumor immunomodulatory roles through the HIF-1-DDX41 cytosolic DNA sensing pathway in HCC (AACR 2024) - "Anti-mitotic agents including Paclitaxel (microtubule stabilizer), Palbociclib (CDK4/6 inhibitor) and AZD1152 and GSK1070916 (Aurora Kinase B inhibitors) can also eliminate cancer cells via an alternative mechanism - the activation of STING signaling. In summary, this study exhibited the novel immune-mediated aspect of cell cycle inhibitors in suppressing tumor growth. Our data suggested the potential combination regimen of cell cycle inhibitors and currently available immunotherapy with promising result."

Immunomodulating • IO biomarker • Hepatocellular Cancer • Oncology • AURKB • DDX41 • HIF1A

Inhibition of Aurora B kinase (AURKB) enhances the effectiveness of 5-fluorouracil chemotherapy against colorectal cancer cells. (PubMed, Br J Cancer) - "AURKB inhibition may be a rational approach to augment the effectiveness of 5-FU chemotherapy in CRC."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • AURKB

Aurora B facilitates cholangiocarcinoma progression by stabilizing c-Myc. (PubMed, Animal Model Exp Med) - "Aurora B plays an essential role in CCA progression by modulating c-Myc stability and represents a new target for treatment and chemosensitization in CCA."

Journal • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • MYC

Aurora kinase B disruption suppresses pathological retinal angiogenesis by affecting cell cycle progression. (PubMed, Exp Eye Res) - "In conclusion, AURKB significantly influenced pathological retinal angiogenesis, thereby presenting a promising therapeutic target in ocular neovascular diseases."

Journal • Oncology • Retinal Disorders • AURKB

AURKA Kinase Controls Erythroblast Enucleation Via Regulation of Centrosome Localization and ECT2 Degradation (ASH 2023) - "Treatment of erythroblasts with MLN8237 (Aliseritib, AURKA selective inhibitor), AZD1152(Barasertib, AURKB selective inhibitor), or AT9283 (AURKA and AURKB inhibitor) dramatically blocked enucleation in a dose-dependent manner. The translocation of AURKA, which is originally restricted to centrosome relied on γ-tubulin interaction during nuclear polarization, was to directly degrade ECT2 at the anterior end of the protrusive nucleus for final nuclear expulsion. Our findings reveal a previously unrecognized localization and role of Aurora kinases in terminal erythroid differentiation and provide new mechanistic insights into erythroblast enucleation."

AURKA • AURKB • PLK4