AZ 628 / AstraZeneca - LARVOL DELTA

Antitumor effects of CEP32496 on urothelial carcinoma with BRAF mutation (V595E) in dogs. (PubMed, Can J Vet Res) - "For reference, 7 BRAF inhibitors, including GDC0879, PLX4720, encorafenib, vemurafenib, dabrafenib, AZ628, and RAF265, were also evaluated. In the xenograft model, 10 mg/kg body weight of CEP32496 resulted in a significant decrease (P < 0.05) in tumor growth in mice, with severe and extensive necrosis on histopathological examination. These results suggested that CEP32496 exerts antitumor effects on both cell proliferation and tumor growth in UC with V595E."

Journal • Oncology • Solid Tumor • Urothelial Cancer • BRAF

Single-cell multi-omics dissection of RevitalAge Markers uncovers age-dependent immunotherapy resistance and druggable targets in melanoma. (PubMed, Biol Direct) - "Drug sensitivity profiling revealed ST3GAL4 exhibited strong correlations with AZ628 (pan-RAF inhibitor) and RDEA119 (MEK inhibitor), which was further validated by molecular docking showing excellent binding affinities (binding energies: -8.7 and - 7.2 kcal/mol). This study provides structural evidence for targeted therapeutic strategies in ST3GAL4-overexpressing melanoma and establishes foundations for age-stratified immunotherapy."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • FDFT1 • GPR143 • IRF8

Combinatorial drug screen identifies therapeutic vulnerabilities of pancreatic cancer subtypes (ESMO-TAT 2026) - "decitabine, oxidative stress inducer elesclomol, and mitogen-activated protein kinase kinase (MEK) inh...rabusertib and AZD7762 ranked among the top combinations with AZD3965...adavosertib also sparked interest, as CHK1 and WEE1 inh... This systematic approach identifies candidate drug pairs for further preclinical testing and highlights translational starting points for developing personalized combination therapies to overcome resistance."

Colon Cancer • Colorectal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CHEK1 • SLC16A1

Prediction of Prognosis, Tumor Microenvironment, and Drug Treatment of Colorectal Cancer Based on Retinoic Acid-Related Genes. (PubMed, J Environ Pathol Toxicol Oncol) - "Drug sensitivity prediction results revealed that AZ628, CGP-082996, CKM, Dasatinib, GNF-2, Saracatinib, Sorafenib, WH-4-023, and WZ-1-84 were more sensitive for patients in the HR group. AKT inhibitor VIII, Gemcitabine, JW-7-52-1, Mitomycin, NSC-87877, PAC-1, Pyrimethamine, QS11, and Roscovitine were more sensitive for those in the LR group. Our project identified correlations between RA-related genes and CRC. The model genes identified are essential indicators for evaluating CRC prognosis and further treating CRC."

Biomarker • Journal • Colorectal Cancer • Oncology • Solid Tumor

Artificial Intelligence Driven Virtual Screening and Molecular Docking Approaches Identified LIFR, BTG2, EPHX2, and PAK3 as Targets and BI-2536, AP-24534, and AZ-628 as Repurposed Drugs for PDAC. (PubMed, IEEE Trans Comput Biol Bioinform) - "The pharmacokinetics study strengthened our results that the identified drugs can be used as a therapeutic for PDAC as they obey Lipinski's rule. In conclusion, identified genes can act as prognostic markers, and drugs could be used as potential therapeutics for PDAC."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BTG2 • LIFR

Multi-omics integrative analysis of stemness-associated pathological signatures to guide prognosis and therapeutic strategies in uveal melanoma. (PubMed, Int J Surg) - "This study highlights a novel integrative framework combining pathomics and scRNA-seq to decode stemness-driven heterogeneity in UVM. The IPS model offers a non-invasive tool for risk stratification and therapeutic guidance, paving the way for precision oncology in rare ocular malignancies. Notably, the IPS was derived and internally validated within a single TCGA-UVM cohort, and its generalizability to other populations requires validation in independent multi-center cohorts."

IO biomarker • Journal • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma

MCLRP: enhanced prediction of anticancer drug response through low-rank matrix completion and transcriptomic profiling. (PubMed, BMC Biol) - "These findings establish MCLRP as a dual-purpose predictive-analytical tool that not only enhances drug response forecasting but also uncovers mutation-specific pharmacological vulnerabilities through systems-level pattern recognition."

Journal • Inflammatory Arthritis • Melanoma • Oncology • Solid Tumor • BRAF • PIK3CA

A fibroblast-specific gene signature as a therapeutic target for glioblastoma developed based on the characteristics of tumor microenvironment. (PubMed, Eur J Med Res) - "We constructed a RiskScore model for predicting the survival outcomes based on fibroblasts-related genes. These findings highlighted the role of fibroblasts in GBM development and offered six potential therapeutic targets (VWA1, DUSP6, LOXL1, IGFBP4, CYGB, and ZIC3) for GBM treatment. Additionally, immune infiltration analysis and drug sensitivity prediction further supported the model's utility in guiding personalized treatment of GBM."

Biomarker • Gene Signature • Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • DUSP6

AZ-628 sensitizes donafenib in hepatocellular carcinoma by targeting tyrosine kinase pathway and ferroptosis. (PubMed, Cytojournal) - "The HCC cells HepG2 and SNU449 were treated with five drugs, namely, dimethyl sulfoxide, AZ-628, SU-5402, TG-101209, and SPP-86, combined with donafenib to determine half-maximal inhibitory concentration values...Ferrous ion (Fe2+) and reactive oxygen species levels were measured after Erastin/RSL3 induction...In vivo experiments demonstrated a combined anti-tumor efficacy of AZ-628 and donafenib in HCC models (P < 0.0001). The findings of this study reveal a new combination therapy targeting the TK pathway for the treatment of HCC and provide a theoretical foundation for addressing donafenib resistance."

Journal • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • EGR1

Identification of SLC7A1 as a potential therapeutic target for high-grade meningioma. (PubMed, Cell Death Discov) - "In brief, our study demonstrated the tumor-promoting function of SLC7A1 by regulating the transcription factors FOXM1 and E2F4 in meningioma and identified SLC7A1 as a potential therapeutic target. Meanwhile, AZ628 is a promising small molecule drug for high-grade meningioma."

Journal • Brain Cancer • Meningioma • Oncology • Solid Tumor • FOXM1

Exploration of prognostic genes associated with lymphangiogenesis in breast cancer based on transcriptomics and experimental verification. (PubMed, PeerJ) - "Additionally, drugs like AUY922 and AZ628 showed considerable potential in treating BC. RT-qPCR results for these four genes in clinical samples aligned with the bioinformatics findings. This study identified and validated four prognostic genes-ZIC2, CD24, CEBPD, and CCL19-that are associated with BC and may provide novel targets for diagnostic and therapeutic strategies."

Biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • BRCA • CCL19 • CD24 • EGFR • ZIC2

Identification of key ferroptosis-related genes associated with the development of gastric cancer: Prognostic models, molecular mechanisms and potential treatment strategies. (PubMed, Oncol Lett) - "Finally, using the Genomics of Drug Sensitivity in Cancer and Cancer Therapeutics Response Portal databases, potential drugs [(5Z)-7-oxozeaenol, selumetinib, RDEA119, AZ628, dabrafenib and trametinib] were identified based on the aforementioned seven key carcinogenic genes, focusing on those that targeted multiple genes. In conclusion, the present study identified 14 key ferroptosis-related genes, and seven key carcinogenic genes, which represent promising novel molecular targets for the prognosis and treatment of GC."

Journal • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • AKR1C2 • GABARAP • GABARAPL2 • GJA1 • MIR484 • MIR675 • NOX4 • NOX5

Exploration of crucial stromal risk genes associated with prognostic significance and chemotherapeutic opportunities in invasive ductal breast carcinoma. (PubMed, J Genet Eng Biotechnol) - "Exploring essential prognostic-risk genes and their association with the prognosis, diagnostic efficacy, and risk-group prediction may provide substantial clues for targeting the breast cancer stromal key-risk genes."

Journal • Breast Cancer • Oncology • Solid Tumor • ADAM8 • CD86 • IGFBP6 • MMP11

Prognosis and immunotherapeutic implications of molecular classification of cervical cancer based on immunophenoscore-related genes. (PubMed, J Biomol Struct Dyn) - "cluster2 had higher immune cell infiltration levels and better prognosis, with greater sensitivity to Cyclopamine, Imatinib, MG-13, Paclitaxel, PHA-665752, Rapamycin, Sorafenib, Sunitinib, and VX-680. In contrast, cluster3 had higher TTN and PIK3CA mutations and greater sensitivity to AZ628, Dasatinib, Doxorubicin, HG-6-64-1, JQ12, Midostaurin, PF-562271, TAE684, and WH-4-023. In conclusion, we developed a feasible risk score model based on IPS-related genes for cervical cancer prognosis and identified potential drugs for different cervical cancer subtypes."

IO biomarker • Journal • Cervical Cancer • Oncology • Solid Tumor • PD-L2 • PIK3CA

BRAF-Mutated Melanoma Cell Lines Develop Distinct Molecular Signatures After Prolonged Exposure to AZ628 or Dabrafenib: Potential Benefits of the Antiretroviral Treatments Cabotegravir or Doravirine on BRAF-Inhibitor-Resistant Cells. (PubMed, Int J Mol Sci) - "Doravirine was particularly effective in reactivating apoptosis and reducing cell growth in highly proliferative resistant cells by increasing tumor-suppressor proteins p16Ink4a and p27Kip1. These findings suggest that antiretroviral drugs can influence apoptosis and cell proliferation in RAF-inhibitor-resistant melanoma cells, offering potential therapeutic strategies for overcoming drug resistance."

Journal • Preclinical • Eye Cancer • Melanoma • Oncology • Retinal Disorders • Solid Tumor • BRAF • CDKN2A

Pan-cancer analysis of oncogenic role of CEP55 and experiment validation in clear cell renal cell carcinoma. (PubMed, Sci Rep) - "We also used Gene Set Cancer Analysis (GSCA) to predict a serious of small molecule CEP55 targeted drugs, such as AZ628, SB52334, SB590885, A-770,041, AZD7762, Elesclomol, panobinostat, BRD-A94377914, and LRRK2-IN-1. Our study indicated that CEP55 overexpression in most caner types was associated with poor prognosis. Notably, CEP55 was closely relevant to immune cell infiltration and impacted the response to immunotherapy and small molecule drugs against cancers."

IO biomarker • Journal • Pan tumor • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CCNA2 • CD4 • CDK1 • CEP55 • KIF11 • LRRK2 • PCNA

Evaluation of the combined antiproliferative effects of Pan-RAF Inhibitor AZ-628 and MEK1 Inhibitor AZD-6244 across a diverse range of tumor cell lines (EORTC-NCI-AACR 2024) - "Our observations of broad synergistic activity of the two compounds suggests that MEK/Raf inhibitor co-treatment could be beneficial for a broader range of cancer types."

Preclinical • Tumor cell • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • BRAF

Multi-omics profiling combined with molecular docking reveals immune-inflammatory proteins as potential drug targets in colorectal cancer. (PubMed, Biochem Biophys Res Commun) - "Drug prediction, coupled with in vitro experiments, suggests that AZ-628 may act as a potential drug to inhibit the proliferation and migration of CRC cell lines HCT-116 and HT-29 by regulating the aforementioned key biological pathways or proteins...This metabolic shift may reflect an adaptive response in cancer cells, favoring specific amino acids to support their growth. Together, these integrated results provide valuable insights into the intricate landscape of tumor development, highlighting the crossroads of immune regulation, cellular structure, and metabolic reprogramming in the tumorigenic process and providing valuable insights into cancer pathology."

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

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

DNA hypomethylation patterns and their impact on the tumor microenvironment in colorectal cancer. (PubMed, Cell Oncol (Dordr)) - "This study unveils a novel epigenetic phenotype in CRC linked to resistance against immune checkpoint inhibitors, presenting a significant step toward personalized medicine by suggesting epigenetic classifications as a means to identify ideal candidates for immunotherapy in CRC. Our findings also highlight potential therapeutic agents for the DMP subtype, offering new avenues for tailored CRC treatment strategies."

Biomarker • IO biomarker • Journal • Tumor microenvironment • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

RAS/RAF/MEK mutated high-grade serous ovarian cancer susceptible to Raf inhibition in vitro but not in vivo (SGO 2024) - "Non-selective (sorafenib, AZ628) and selective (GW5074, dabrafenib) RAFi were added in serial concentrations to each cell line and incubated for 48-96 hours. cBioPortal data mining identified a HGSOC subpopulation hypothesized to be uniquely susceptible to RAFi. The RAS/RAF/MEK pathway phenotype in this subpopulation was replicated in the human derived OV-90 cell line. While non-selective RAFi demonstrate in vitro antitumor activity, a paradoxical effect was observed in vivo, with accelerated tumor growth in the treated arms."

Preclinical • Melanoma • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • BRAF • KRAS

Integrative Analysis of Machine Learning and Molecule Docking Simulations for Ischemic Stroke Diagnosis and Therapy. (PubMed, Molecules) - "AZ_628, which screened from CMap analysis, was found to have lower binding energy with Mmp12, Lgals3, Fam20c, Capg, Pkm2, Sdc4, and Itga5 in microglia subcluster 2 and maybe a therapeutic agent for the poor development of microglia subcluster 2 after stroke. Our study presents a nomogram model for stroke diagnosis and provides a potential molecule agent for stroke therapy."

Journal • Machine learning • Cardiovascular • Ischemic stroke • ITGA5 • LGALS3 • PKM • SDC4

Immune activity score to assess the prognosis, immunotherapy and chemotherapy response in gastric cancer and experimental validation. (PubMed, PeerJ) - "In addition, resistance to Erlotinib, Rapamycin, MG-132, Cyclopamine, AZ628, and Sorafenib was reduced in patients with low IAS. For GC patients, IAS showed excellent robustness in predicting GC prognosis, immune activity status, immunotherapy response, and chemotherapeutic drug resistance. Our study provided novel insights into the prognostic assessment in GC."

IO biomarker • Journal • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CTLA4 • NPC2 • SLC2A3

A novel prognostic N-methylguanosine-related long non-coding RNA signature in clear cell renal cell carcinoma. (PubMed, Sci Rep) - "High-risk group of patients was more susceptible to A.443654, A.770041, ABT.888, AMG.706, and AZ628. Quantitative real-time polymerase chain reaction (qRT-PCR) exhibited that the expression levels of LINC01507, AC093278.2 were very high in all five ccRCC cell lines, AC084876.1 was upregulated in all ccRCC cell lines except 786-O, and the levels of AL118508.1 and DUXAP8 were upregulated in the Caki-1 cell line. This risk model may be promising for the clinical prediction of prognosis and immunotherapeutic responses in patients with ccRCC."

IO biomarker • Journal • Tumor mutational burden • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • DUXAP8 • TMB

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