AZD8055 / AstraZeneca - LARVOL DELTA

Targeting tumour-astrocyte crosstalk for rational identification of novel therapeutic targets for medulloblastoma and atypical teratoid/ rhabdoid tumours (SNO 2025) - "3D migration studies found that T-5224 (FOS inhibitor) and AZD8055 significantly reduced migration of spheroids in vitro for MB cells.Delivery of T-5224 and AZD8055 to a d425 resection model demonstrated tolerability. Similarly, delivery of Tiplaxtinin and AZD8055 conferred tolerability in a BT12 resection model and a survival advantage was indicated in groups treated with AZD8055 alone."

Brain Cancer • Medulloblastoma • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor • COL1A1 • MMP2 • NOTCH3 • S100A10 • SERPINE1 • SOCS3 • TGFBR2

Treatment with L-type amino acid transporter 1 inhibitor JPH203 enhances protein synthesis in C2C12 myotubes. (PubMed, Sci Rep) - "ATP-competitive mTOR inhibitor AZD8055 (1 μM) suppressed JPH203-induced protein synthesis. JPH203 treatment increased intracellular glutamine concentration. These results suggest that inhibition of LAT1 function augments muscle protein synthesis, possibly through the activation of rapamycin-insensitive mTOR signaling; elevated intracellular glutamine levels may contribute to the enhancement of muscle protein synthesis induced by LAT1 inhibition."

Journal • EIF4EBP1

Targeting tumour-astrocyte crosstalk for rational identification of novel therapeutic targets for medulloblastoma and atypical teratoid/ rhabdoid tumours (WFNOS 2025) - "3D migration studies found that T-5224 (FOS inhibitor) and AZD8055 significantly reduced migration of spheroids in vitro for MB cells.Delivery of T-5224 and AZD8055 to a d425 resection model demonstrated tolerability. Similarly, delivery of Tiplaxtinin and AZD8055 conferred tolerability in a BT12 resection model and a survival advantage was indicated in groups treated with AZD8055 alone."

Brain Cancer • Medulloblastoma • Rhabdoid Tumor • Sarcoma • Solid Tumor • COL1A1 • MMP2 • NOTCH3 • S100A10 • SERPINE1 • SOCS3 • TGFBR2

Identification of prognostic genes associated with sphingosine-1-phosphate in gastric cancer to construct a risk mode. (PubMed, Transl Cancer Res) - "Finally, the half-maximal inhibitory concentrations (IC50) values of AZD8055 and docetaxel drugs were found to be lower in the high-risk group, when compared with the low-risk group. Seven prognostic genes that were associated with S1P, in GC, were investigated by constructing a risk model, which may provide clinical significance for the treatment of GC."

Journal • Gastric Cancer • Oncology • Solid Tumor

Comparison of the effects of rapamycin and AZD8055 on colon cancer cells through UPLC-MS/MS-based metabolomics. (PubMed, J Pharm Biomed Anal) - "Concurrently, a marked increase in taurine levels was observed in the AZD8055 group, further enhancing its antioxidant and anti-tumor effects. Although both compounds similarly inhibited branched-chain amino acid (BCAA) metabolism, comprehensive metabolic analysis revealed that AZD8055 has greater potential in modulating tumor metabolic pathways, thereby providing new theoretical support for the translational development of mTORC1/2 dual inhibitors."

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

Integrative Analysis of TLS-Associated Gene Signatures, Immune Infiltration and Drug Sensitivity in Pancreatic Cancer. (PubMed, IET Syst Biol) - "Notably, the TLS_H group demonstrated enhanced sensitivity to chemotherapeutics including AZD8055, axitinib, vorinostat, nilotinib, camptothecin and paclitaxel. Real-time fluorescent quantitative PCR (RT-qPCR) validation in Mia PaCa2 and Jurkat cells indicated that LAT, RBP5 and SKAP1 may play important roles in modulating sensitivity to these chemotherapeutics. These findings establish TLS as a potential biomarker for PAAD, enabling personalised chemotherapy selection by integrating immune contexture and genomic drivers to improve clinical outcomes."

Gene Signature • Journal • Tumor mutational burden • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CCR6 • CD1D • CD79B • PTGDS • SKAP1 • TMB

SINGLE CELL FIXED RNA-SEQUENCING ANALYSIS REVEALED HSCSLMCD1+ IS A DRIVER OF LIVER FIBROSIS BY MODULATING AKT-PRAS40-4EBP1 (AASLD 2025) - "Specific pathways inhibition using AZD8055 mitigated HSCs activation, both spontaneously and under TGF-β stimulation, and significantly reduced the phosphorylation of 16/39 proteins implicated in HSC activation, including CREB, c-JUN, TP53, WNK1, GSK3B, ERK1/2, P70S6K, and RSK1/2/3... Our single-cell transcriptomic atlas reveals the cellular and molecular reprogramming underpinning fibrosis progression and regression in the liver. HSC subclustering revealed novel activation marker LMCD1, upregulated during fibrosis and reduced in regression via LMCD1-AKT-PRAS40-4EBP1 axis. These findings provide a foundation for the development of targeted therapies aimed at mitigating liver fibrosis and its progression."

Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatotic Liver Disease • AKT1S1 • EIF4EBP1 • JUN • PDLIM5 • PDLIM7 • TGFB1 • TP53 • UNC13D • WNK1

Integrated single-cell and bulk RNA-sequencing data reveal prognosis and therapeutic response in low-grade glioma based on hypoxia-lactylation related genes. (PubMed, Discov Oncol) - "The constructed 4-gene hypoxia-lactylation prognostic model can effectively predict survival risk in LGG patients. The high-risk group is characterized by activation of pro-tumorigenic pathways, high immune infiltration, and sensitivity to specific targeted drugs. FABP5 + TAMs participate in LGG progression by regulating lipid metabolism and inflammatory responses, representing a potential therapeutic target."

Journal • Brain Cancer • Glioma • Metabolic Disorders • Oncology • Solid Tumor • FABP5 • KIF2C • SERPINE1 • SLC16A1

Immune Evasion Mechanism Mediated by ITPRIPL1 and Its Prognostic Implications in Glioma. (PubMed, Brain Behav) - "This study reveals that ITPRIPL1 plays a dual role in glioma: It suppresses T cell-mediated immune responses, contributing to an immunosuppressive microenvironment, and interferes with the efficacy of antitumor drugs, thereby promoting tumor progression and ultimately leading to poor patient prognosis."

IO biomarker • Journal • Brain Cancer • Glioma • Oncology • Solid Tumor • CD4

Antitumor Effect of mTOR1/2 Dual Inhibitor AZD8055 in Canine Pulmonary Carcinoma. (PubMed, Cancers (Basel)) - "Three canine PC cell lines (AZACL1, AZACL2, and cPAC-1) were treated with three mTOR inhibitors (AZD8055, temsirolimus, and everolimus). In xenograft mice injected with the AZACL1 and AZACL2 cell lines we showed that the AZD8055-treated group exhibited a significant reduction in tumor volume via the inhibition of tumor growth compared to the control group. These findings reveal that the PI3K/AKT/mTOR pathway plays a key role in canine PC and that AZD8055 may be a novel therapeutic agent for PC-bearing dogs."

Journal • Lung Adenocarcinoma • Lung Cancer • Oncology • Palliative care • Solid Tumor

Unraveling the Role of TARGET OF RAPAMYCIN in the Immune Response of Cucumis sativus to Podosphaera xanthii. (PubMed, Physiol Plant) - "In this study, cucumber seedlings were treated with AZD8055, a TOR-specific inhibitor, and subsequently challenged with P. xanthii. Overall, bHLH35 and FLZ15 likely drive immune function due to the action of TOR. Our findings elucidate the molecular events by which TOR modulates plant disease resistance in P. xanthii-infected cucumbers."

Journal • Infectious Disease

S1PR4 promotes cell viability, invasion and glycolysis via the mTOR signaling pathway in endometriosis. (PubMed, Gynecol Obstet Invest) - "In endometriosis, S1PR4 enhances cellular glycolysis by activating the mTOR signaling pathway, thereby promoting the viability and invasion of EESCs."

Journal • Endometriosis • Gynecology • Infertility • Sexual Disorders • Women's Health • LDHA

Enhancing microspore embryogenesis initiation by reducing ROS, autophagy, and cell death with novel small molecules in rapeseed and barley. (PubMed, J Plant Physiol) - "We identified novel small molecule antioxidants that mitigated these effects, enhancing cell viability and promoting microspore embryogenesis initiation. The findings in two phylogenetically distant crop species suggest a conserved cellular response and highlight the potential of these compounds to improve in vitro protocols in other species where early-stage cell death poses a significant challenge during embryogenesis induction."

Journal

Selection and validation of reference genes for RT-qPCR normalization in dormant cancer cells. (PubMed, Sci Rep) - "To prevent incorrect selection of a reference gene in dormant tumor cells, we analyzed the expression stability of the widely used housekeeping genes GAPDH, ACTB, TUBA1A, RPS23, RPS18, RPL13A, PGK1, EIF2B1, TBP, CYC1, B2M, and YWHAZ in the T98G, A549, and PA-1 cancer cell lines treated with the dual mTOR inhibitor AZD8055...The optimal reference genes among the 12 candidate reference genes were not revealed in the PA-1 cell line. Validation of the stability of the 12 investigated genes demonstrated that the incorrect selection of a reference gene resulted in a significant distortion of the gene expression profile in dormant cancer cells."

Journal • Oncology • B2M • EIF2B4 • GAPDH • PGK1 • RPL13A • RPS23 • TUBA1A • YWHAZ

Drug sensitivity patterns across FAB subtypes and molecular mutations in AML. (ASCO 2025) - "M1 samples (n=22 patients) demonstrated higher sensitivity to Navitoclax (σsDSS = 15.89), while combinations with mTOR inhibitors like Navitoclax + PF-04691502 (σsDSS = 13.97) and Navitoclax + Vistusertib (σsDSS = 13.72) showed promise...M4 subtypes (n=2 patients) were most sensitive to BAY 87-2243 (σsDSS = 15.98), with dual combinations like BAY 87-2243 + Cerdulatinib (σsDSS = 14.21) and BAY 87-2243 + Pevonedistat (σsDSS = 14.13) maintaining strong responses...In M4 eos (n=9 patients), Pimasertib demonstrated notable effectiveness (σsDSS = 14.43), with dual-agent combination such as Pimasertib + SCH772984 (σsDSS = 14.24) supporting RAS/ERK pathway inhibition. Despite rare M4/M5 subtypes (n=2 patients) showing limited Refametinib sensitivity (σsDSS = 8.75), their minimal sample size precludes definitive conclusions...Likewise, mutation analysis revealed that NPM1-mutated samples showed increased sensitivity to Venetoclax (σsDSS = 13.28) and PF-04691502 (σsDSS =..."

Acute Myelogenous Leukemia • FLT3 • NPM1

mTOR blockade mitigates chemotherapy drug-induced intestinal toxicity via inhibition of pyroptosis. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "In this study, we demonstrate that mTOR signaling blockade can mitigate etoposide- or cisplatin-induced intestinal injury in mice. Importantly, although AZD8055 counteracts the side effects of chemotherapy drugs, it does not substantially affect their anti-tumor activity. Our study proposes the potential application of mTOR inhibitors as chemoprotective agents, presenting a means to prolong the duration of chemotherapy drug use and optimize the chemotherapeutic regimen."

Journal • Oncology • CASP3 • GSDME • HMGB1

Synthesis and Biological Evaluation of MEK/mTOR Multifunctional Inhibitors as Novel Anticancer Agents. (PubMed, J Med Chem) - "The mitogen-activated protein kinase (MAPK) and mechanistic target of rapamycin (mTOR) signaling nodes play a crucial role in many human cancers...A series of mTOR inhibitor analogs of AZD8055 and AZD2014 were designed to allow for covalent linking to a potent MAPK kinase (MEK) inhibitor to produce a single, bivalent chemical entity...Additionally, compound LP-65 demonstrated significant modulation of MEK and mTOR signaling activity in human glioma cells (D54) and human melanoma cells (A375), with a corresponding decrease in cellular proliferation and migration. Treatment of mice with LP-65 (40 mg/kg) having a myeloproliferative neoplasm, myelofibrosis, revealed down modulation of in vivo signaling pathways and therapeutic efficacy."

Journal • Brain Cancer • Glioma • Melanoma • Myelofibrosis • Myeloproliferative Neoplasm • Oncology • Solid Tumor

Harnessing Calmodulin-Related Genes to Build a Prognostic Model in Esophageal Squamous Cell Carcinoma for a Comprehensive Analysis of Single-Cell Immune Characteristics and Drug Efficacy. (PubMed, J Immunother) - "The CETSA experiment demonstrated the existence of a favorable binding thermal stability between AZD-8055 and MYO1G. This research may identify potential biomarkers for predicting the prognosis of ESCC patients."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • CALB1 • KCNQ1OT1

A prognostic glycolysis-related gene signature in osteosarcoma: implications for metabolic programming, immune microenvironment, and drug response. (PubMed, PeerJ) - "Moreover, a significant disparity in drug sensitivity to AZD8055, paclitaxel, and PD0325901 was noted between the high-risk and low-risk cohorts, and the established four-gene risk signature served as dependable prognostic indicators in the validation cohort, confirmed at the cellular level through external dataset validation and reverse transcription quantitative PCR (RT-qPCR) experiments. A risk signature based on GRGs was established for OS, exhibiting robust predictive efficacy for prognostic assessment, and offering significant clinical utility for the prognosis of OS."

Biomarker • Gene Signature • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • RAS • RRAGD • TPR • VCAN

NF1 mutations in lung adenocarcinoma preclinical models and potential targeted therapies: The crucial role of the RAS-MAPK pathway (AACR 2025) - "No sensitivity was observed in these models when treated with the mTOR inhibitor AZD8055 or the PI3K inhibitor Buparlisib alone. We then performed in vivo pharmacological tests on the LUAD PDX: Trametinib alone and in combination with Buparlisib resulted in significant tumor volume reductions of 72% and 84%, respectively. Collectively, these findings establish a promising possible efficacy of MEK inhibitors for LUAD patients with NF1 homozygous mutation."

Preclinical • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • NF1

Single cell fixed RNA-seq revealed HSCLMCD1+LIMK2+ is a driver of liver fibrosis by modulating SMAD3-AKT-PRAS40-4EBP1 (EASL 2025) - "Specific inhibition using AZD8055 mitigated HSC activation, both spontaneously and under TGF-β stimulation, and significantly reduced the phosphorylation of 16/39 proteins implicated in HSC activation, including CREB, c-JUN, TP53, WNK1, GSK3B, STAT2/3, HSP27/60, and RSK1/2/3... This study highlights previously unrecognized molecular and cellular dynamics of HSCs, identifying LMCD1 and LIMK2 as promising therapeutic targets for antifibrotic interventions."

Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatotic Liver Disease • AKT1S1 • EIF4EBP1 • ETV4 • FOSL1 • GATA2 • GATA3 • JUN • PDLIM5 • PDLIM7 • SMAD3 • STAT2 • TGFB1 • TP53 • UNC13D • VIM • WNK1

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

The miR-451a facilitates natural killer cell-associated immune deficiency after ischemic stroke. (PubMed, J Cereb Blood Flow Metab) - "Pharmacological inhibition of Akt-mTOR pathway with AZD8055 effectively blocked the impacts of miR-451a on NK cell functions. Collectively, these findings suggest miR-451a negatively regulates NK cell cytotoxicity in both the brain and periphery, which could be re-addressed by modulating the Akt-mTOR signaling pathway."

Journal • Cardiovascular • CNS Disorders • Infectious Disease • Inflammation • Ischemic stroke • CD69 • IFNG • MIR451A

Silencing fatty acid-binding protein 4 improved sepsis-induced myocardial dysfunction through anti-apoptotic and antioxidant effects by mammalian target of rapamycin signaling pathway. (PubMed, Cytojournal) - "However, the therapeutic effect was inhibited when FABP4 silencing was combined with the mTOR inhibitor AZD-8055. Silencing FABP4 alleviates LPS-induced inflammatory response and apoptosis in H9c2 cells and enhances mitochondrial function through the mTOR signaling pathway."

IO biomarker • Journal • B Cell Lymphoma • Infectious Disease • Lymphoma • Oncology • Septic Shock • BAX • FABP4

An mTOR inhibitor discovery system using drug-sensitized yeast. (PubMed, Geroscience) - "Inhibition of the target of rapamycin (TOR/mTOR) protein kinase by the drug rapamycin extends lifespan and health span across diverse species...In contrast, 100 nM Torin1 and 500 nM GSK2126458 (omipalisib) are sufficient to identify TOR1-dependent growth inhibition in the drug-sensitized background...Additionally, for the TOR inhibitor AZD8055, the drug-sensitive system resolves that the compound results in TOR1-dependent growth sensitivity at 100 µM, whereas no growth inhibition is observed in a wild-type yeast strain background. Our platform also identifies the caffeine analog aminophylline as a TOR1-dependent growth inhibitor via selective tor1 growth sensitivity. We also tested nebivolol, isoliquiritigenin, canagliflozin, withaferin A, ganoderic acid A, and taurine and found no evidence for TOR inhibition using our yeast growth-based model. Our results demonstrate that this system is highly effective at identifying compounds that inhibit the TOR..."

Journal • Oncology