AZD6482 / AstraZeneca, Wuhan University, ThromBio - LARVOL DELTA

Integrated multi-omics analysis and machine learning refine molecular subtypes and clinical outcome for hepatocellular carcinoma. (PubMed, Hereditas) - "Encouragingly, we observed that the high-CMLBS patients may exhibit increased sensitivity to Alpelisib, AZD7762, BMS-536,924, Carmustine, and GDC0810, whereas they may demonstrate reduced sensitivity to Axitinib, AZD6482, AZD8055, Entospletinib, GSK269962A, GSK1904529A, and GSK2606414, suggesting that CMLBS may contribute to the selection of chemotherapeutic agents for HCC patients. Therefore, in-depth examination of data from multi-omics data can provide valuable insights and contribute to the refinement of the molecular classification of HCC. In addition, the CMLBS model demonstrates potential as a screening tool for identifying HCC patients who may derive benefit from immunotherapy, and it possesses practical utility in the clinical management of HCC."

Clinical data • Journal • Hepatocellular Cancer • Oncology • Solid Tumor

PI3Kβ inhibitor mediated immune evasion in PTEN/Trp53 double knockout prostate cancer (AUA 2025) - "Our findings suggest that PI3Kβ inhibition can effectively convert "cold" prostate cancer into immune-infiltrated ones in Pten and Trp53-deficient prostate cancer. The specific mechanism is by promoting T cell infiltration and dendritic cell maturation, while decreasing MDSC and Treg.Our study provides a strong rationale for combining AZD6482 with anti-PD-1 therapy in the treatment of PTEN and Trp53-defcient prostate cancer."

IO biomarker • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • CD8 • IFNA1 • PIK3CB • PTEN • PTPRC • TP53

Construction of CD8+ T Cell-Associated Risk Model in Hepatocellular Carcinoma Based on Bulk and Single-Cell RNA-Seq Data (APASL 2025) - "BMS-754807, Gemcitabine, et al exhibited sensitive to patients in low-risk group, AZD6482 and SB505124 may serve as novel potential targeted drugs for patients in high-risk group. A CD8+ T cell-associated risk scoring model consisting of KLRB1, RGS2 and TNFRSF1B has been developed to predict prognosis and provide potential drugs for HCC treatment. Table and Figure:Figure 1."

IO biomarker • Hepatocellular Cancer • Hepatology • Oncology • Solid Tumor • CD8 • KLRB1 • RGS2 • TNFRSF1B

Co-STARS: Safety, Tolerability and Efficacy of Adjunctive TBO-309 in Reperfusion for Stroke with Tandem Occlusion (clinicaltrials.gov) - P2 | N=78 | Not yet recruiting | Sponsor: ThromBio Pty. Ltd.

New P2 trial • Cardiovascular • Ischemic stroke

A Novel Mitochondrial-Related Gene Signature for the Prediction of Prognosis and Therapeutic Efficacy in Lower-Grade Glioma. (PubMed, Biochem Genet) - "Finally, using data from the CTRPv2 and GDSC2 datasets to assess chemotherapy response in LGG, it was predicted that the chemotherapeutic agents AZD6482, MG-132, and PLX-4720 might be potential agents for patients in the high-MiAS group of LGG. In contrast, overexpression of OCIAD2 enhanced these abilities of glioma cells. This study found that MRGs were correlated with LGG patient prognosis, which is expected to provide new treatment strategies for LGG patients with different MiAS."

Gene Signature • IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor

Machine learning-based integration develops a multiple programmed cell death signature for predicting the clinical outcome and drug sensitivity in colorectal cancer. (PubMed, Anticancer Drugs) - "In addition, the high-MPCDI group was more sensitive to AZD1332, Foretinib, and IGF1R_3801, and insensitive to AZD3759, AZD5438, AZD6482, Erlotinib, GSK591, IAP_5620, and Picolinici-acid, which suggests that the MPCDI can guide drug selection for CRC patients. As a new clinical classifier, the MPCDI can more accurately distinguish CRC patients who benefit from immunotherapy and develop personalized treatment strategies for CRC patients."

Clinical data • Journal • Machine learning • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

m6A- and m5C- modified lncRNAs orchestrate the prognosis in cutaneous melanoma and m6A- modified LINC00893 regulates cutaneous melanoma cell metastasis. (PubMed, Skin Res Technol) - "We made an analysis of m6A- and m5C- related lncRNAs in melanoma samples and a prediction of these lncRNAs' role in prognosis, tumor microenvironment, immune infiltration, and clinicopathological features. We also found that LINC00893, which is potentially regulated by m6A modification, could serve as a tumor-suppressor in melanoma and play an inhibitory role in melanoma metastasis."

Biomarker • Journal • Cutaneous Melanoma • Melanoma • Oncology • Solid Tumor • AGAP2-AS1 • METTL3 • MIAT • SEMA6A • YTHDF3

Integrated analysis of histone modification features in clear cell renal cancer for risk stratification and therapeutic prediction. (PubMed, Transl Oncol) - "Patients with low HiMG may be potential responders to rapamycin, erlotinib and FH535, while AZD6482 and CHIR-99,021 may be more suitable for patients with high HiMG levels. ccRCC histone modification distribution and a clinical signature for prognosis prediction, clinical decision making, and molecular mechanism exploration, were established for risk stratification and personalized treatments."

Epigenetic controller • IO biomarker • Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • Urethral Cancer • Urology • CKS2 • PD-1

Identification of a Macrophage marker gene signature to evaluate immune infiltration and therapeutic response in hepatocellular carcinoma. (PubMed, Heliyon) - "Moreover, a low-Macrosig score indicates increased sensitivity to AZD.2281, A.443654, ABT.263, ABT.888, AG.014699 and ATRA, while a high Macrosig score indicates increased sensitivity to AZD6482, AKT inhibitor VIII, AS601245, AZ628, AZD.0530 and AZD6244. A novel scoring system was constructed to guide more effective prognostic evaluation and tailoring therapeutic regimens for HCC patients."

Gene Signature • IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • LAG3 • PD-1 • TIGIT

Bioinformatics Identification and Experimental Validation of a Prognostic Model for the Survival of Lung Squamous Cell Carcinoma Patients. (PubMed, Biochem Genet) - "For patients with high-risk LUSC, we discovered seven potent potential drugs (AZD6482, CHIR.99021, CMK, Embelin, FTI.277, Imatinib, and Pazopanib). In conclusion, the cuproptosis-based genes predictive risk model can be utilized to predict outcomes, track immune function, and evaluate medication sensitivity in LUSC patients."

Journal • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma

SAFETY AND TOLERABILITY OF ADJUNCTIVE TBO-309 IN REPERFUSION FOR STROKE (STARS), TRIAL UPDATE (ESOC 2024) - P2 | "If the trial shows safety of the AZD6482, further trials will be conducted to assess its efficacy."

Clinical • Cardiovascular • Ischemic stroke • Thrombosis

Comprehensive analysis of T cell exhaustion related signature for predicting prognosis and immunotherapy response in HNSCC. (PubMed, Discov Oncol) - "In conclusion, we developed a novel T cell exhaustion-associated signature, which holds considerable predictive value for both the prognosis of patients with HNSCC and the effectiveness of tumor immunotherapy."

IO biomarker • Journal • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • TAF1

Complement and coagulation cascades are associated with prognosis and the immune microenvironment of lower-grade glioma. (PubMed, Transl Cancer Res) - "By means of oncoPredict, MG-132, BMS-536924, PLX-4720, and AZD6482 were identified as potential sensitive drugs for high-risk patients, of which MG-132 was particularly recommended for high-risk patients. We performed in vitro experiments to explore the anti-glioma effect of MG-132, and the results demonstrated MG-132 could inhibit the proliferation and migration of glioma cells. Our findings show that CCC genes are associated with the prognosis and immune infiltration of LGG and provide possible immunotherapeutic and novel chemotherapeutic strategies for patients with LGG based on the risk signature."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • SERPINA1

A novel stratification framework based on anoikis-related genes for predicting the prognosis in patients with osteosarcoma. (PubMed, Front Immunol) - "The low-risk group was sensitive to the immune checkpoint PD-1 inhibitor, and the high-risk group exhibited lower inhibitory concentration values by 50% for 24 drugs, including AG.014699, AMG.706, and AZD6482. The prognostic stratification framework of patients with OS based on ARGs, such as BNIP3 and CXCL12, may lead to more efficient clinical management."

IO biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CXCL12

Identification of Macrophage Associated Gene Landscape to Evaluate Immune Infiltration and Therapeutic Response in Hepatocellular Carcinoma (APPLE 2023) - "A novel scoring system based on macrophage subclusters was constructed, thereby guiding more effective prognostic evaluation and tailored potential drug agents strategies of HCC patients."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Immune Modulation • Oncology • Solid Tumor • LAG3 • PD-1 • TIGIT

Co-targeting CK1epsilon and PIK3CB/p110beta to treat glioblastoma (AACR 2023) - "It is therefore imperative to investigate if co-targeting CK1epsilon and PIK3CB/p110β yields a synergistic inhibitory effect on GBM cell growth.GBM cells were treated with either DMSO (control), IC261 (chemical inhibitor of CK1epsilon), AZD6482 (chemical inhibitor of PIK3CB/p110β), or both IC261 and AZD6482...To further elucidate the mechanism of GBM cell death, immunoblotting will also be performed to detect β-catenin activity after inhibition of CK1epsilon and PIK3CB/p110β. Overall, preliminary results show that co-inhibition of CK1epsilon and PIK3CB/p110β with chemical inhibitors yields synergistic GBM cell death."

Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor • PIK3CB

Synthetic methodologies and SAR of quinazoline derivatives as PI3K inhibitors. (PubMed, Anticancer Agents Med Chem) - "Lapatinib, afatinib, gefitinib, erlotinib, idelalisib and copanlisib are quinazoline-based, FDA-approved PI3K inhibitors, while compounds like NVPBYL719, GDC-0032, AZD8186, AZD-6482, etc. are under different stages of clinical trials. In light of the above-mentioned facts, in the present study, we have reported different synthetic approaches, mechanisms of anticancer action, and structure-activity relationship analysis of reported quinazoline derivatives as PI3K inhibitors to help researchers working in the field in designing better and isoform-selective PI3K inhibitors."

Journal • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

HOXB13/IL17RB-low breast cancers are predicted to respond to PIK3CA inhibitors independent of PIK3CA mutational status (SABCS 2022) - "No-significant associations between the PPI dysreg magnitude of the drug-associated leading-edge genes and PIK3CA mutational status was observed (AZD6482 FDR=0.736 and A66 FDR=0.95). No significant genetic alteration, including PIK3CA mutational status, was identified between H/I-high and H/I-low groups. Thus, protein- protein interaction (PPI) dysregulation analysis identifies H/I-low BC tumors as those that are predicted to response to PIK3CA inhibitors independent of PIK3CA mutational status."

Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA2 • CCND1 • CDH1 • FGF19 • HER-2 • HOXB13 • IL17RB • PIK3CA • TP53

Optimization of potential non-covalent inhibitors for the SARS-CoV-2 main protease inspected by a descriptor of the subpocket occupancy. (PubMed, Phys Chem Chem Phys) - "Our results suggest that fusidic acid, polydatin, SEN-1269, AZD6482, and UNC-2327 have high binding affinities of more than 23 kcal mol...The molecular optimization of ADZ6482 via reinforcement learning algorithms was carried out to screen out three lead compounds, in which slight structural changes give more considerable binding energies and an occupancy of the S4 subpocket of up to 43%. The energetic occupancy could be a useful descriptor for evaluating the local binding affinity for drug design."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Evaluating the role of the PIK3CB pathway in temozolomide resistance in glioblastoma using the Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Cell Line Encyclopedia (CCLE) databases (SNO 2022) - "We found that AKT phosphorylation and PIK3CB mRNA data together performed better as a biomarker in predicting therapeutic response to p110β-selective inhibitors than each variable alone, specifically we found that AKT phosphorylation at T308 was negatively related to p110β-selective inhibitor AZD6482 sensitivity at low PIK3CB expression levels (B = -0.069, p = 0.0513) and this relationship disappeared at higher expression levels (B = 0.04, p = 0.176) with an interaction at near statistical significance (p = 0.0674). While AKT phosphorylation is currently used as a biomarker for PI3K pathway inhibitors, in this study, we demonstrate that both PIK3CB mRNA and AKT phosphorylation together was a significant biomarker in sensitivity to p110β inhibitors as compared to assessing each independently. Furthermore, PIK3CB was implicated in TMZ resistance in GBM as compared to other catalytic isoforms."

Preclinical • Brain Cancer • Glioblastoma • Inflammatory Arthritis • Oncology • Solid Tumor • PIK3CB

STARS: Safety and Tolerability of AZD6482 in Reperfusion for Stroke (clinicaltrials.gov) - P2 | N=80 | Not yet recruiting | Sponsor: The George Institute | Initiation date: Oct 2022 ➔ Apr 2023

Trial initiation date • Cardiovascular • Ischemic stroke • Solid Tumor

PD-L1-Mediated Immunosuppression in Hepatocellular Carcinoma: Relationship with Macrophages Infiltration and Inflammatory Response Activity. (PubMed, Biomolecules) - "Notably, given the immunosuppressive and inflammatory microenvironment in HCC, we screened four candidate drugs, including dasatinib, vemurafenib, topotecan and AZD6482, and corroborated in two pharmacogenomics databases, which might have potential therapeutic implications in specific HCC patients. Our results enhanced the understanding of linkage in PD-L1 expression patterns with macrophages and inflammation, which may provide new insight into the pathogenic mechanisms and potential therapeutic strategy for HCC."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Immunology • Inflammation • Oncology • Solid Tumor • PD-L1

Novel Diagnostic and Therapeutic Options for KMT2A-Rearranged Acute Leukemias. (PubMed, Front Pharmacol) - "We observed that KMT2A-r cell lines were more sensitive to 5-Fluorouracil (5FU), Gemcitabine (both antimetabolite chemotherapy drugs), WHI-P97 (JAK-3 inhibitor), Foretinib (MET/VEGFR inhibitor), SNX-2112 (Hsp90 inhibitor), AZD6482 (PI3Kβ inhibitor), KU-60019 (ATM kinase inhibitor), and Pevonedistat (NEDD8-activating enzyme (NAE) inhibitor). Moreover, IC50 data from analyses of ex-vivo drug sensitivity to small-molecule inhibitors reveals that Foretinib is a promising drug option for AML patients carrying FLT3 activating mutations. Thus, we provide novel and accurate options for the diagnostic screening and therapy of KMT2A-r leukemia, regardless of leukemia subtype."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • CSPG4 • FLT3 • JAK3 • KMT2A • PIK3CB

Integrative metabolomics and transcriptomics analysis reveals novel therapeutic vulnerabilities in lung cancer. (PubMed, Cancer Med) - "We demonstrated the clinical utility of this integrated metabolic gene signature in LUAD by using it to guide repurposing of AZD-6482, a PI3Kβ inhibitor which significantly inhibited three genes from the 28-gene signature. Overall, we have integrated metabolomics and transcriptomics analyses to show that LUAD and LUSC have distinct profiles, inferred gene signatures with prognostic value for patient survival, and identified therapeutic targets and repurposed drugs for potential use in NSCLC treatment."

Journal • Lung Adenocarcinoma • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PIK3CB

SAFETY AND TOLERABILITY OF AZD6482 IN REPERFUSION FOR STROKE (STARS) (ESOC 2022) - "If the trial shows safety of the AZD6482, further trials will be conducted to assess its efficacy."

Clinical • Cardiovascular • Ischemic stroke • Thrombosis