saracatinib (AZD0530) / AstraZeneca - LARVOL DELTA

Dual Inhibition of SRC Family Kinases and Sorafenib Enhances Anti-Tumor Activity in Hepatocellular Carcinoma Cells. (PubMed, Int J Mol Sci) - "To evaluate the efficacy of dual targeting, we assessed the combination between SRC inhibitors, saracatinib and dasatinib, with sorafenib in six hepatic cell models, representing both S1 and S2 subtypes. Additionally, combined therapies decreased VEGFA and HIF1A expression compared to sorafenib alone, suggesting a potential to counteract the adaptive resistance mechanisms of cells to sorafenib. In summary, the combination of SFK inhibitors with sorafenib significantly enhances anti-tumor activity, offering a promising strategy to address HCC cellular heterogeneity and improve treatment efficacy."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • HIF1A • MMP2 • MMP9

Hepatic stellate cell TM4SF1 accelerates hepatic fibrosis progression via interacting with the tyrosine kinase c-Src. (PubMed, Cell Mol Gastroenterol Hepatol) - "TM4SF1 promotes HF progression and HSC activation by binding to and activating c-Src. TM4SF1 could be a future therapeutic target for HF by inhibiting HSC activation."

Journal • Fibrosis • Hepatology • Immunology • Oncology • Solid Tumor • IFIT3 • TM4SF1

Diet-incorporated saracatinib, a Src tyrosine kinase inhibitor, counteracts diisopropylfluorophosphate (DFP)-induced chronic neurotoxicity in the rat model. (PubMed, Biomed Pharmacother) - "These findings underscore the complex relationship between the early markers of epileptogenesis and the disease-modifying potential of SAR-in-diet. Additionally, the SAR-in-diet treatment approach is translational and reduces handling stress in animals in long-term studies."

Journal • Preclinical • CNS Disorders • Epilepsy • Inflammation • CD68 • GFAP • HCK • IL17A • IL18 • IL6 • TNFA

Lactate-Activated GPR132-Src Signal Induces Macrophage Senescence and Aggravates Atherosclerosis Under Diabetes. (PubMed, Adv Sci (Weinh)) - "Furthermore, saracatinib, a specific Src inhibitor, has been demonstrated to effectively alleviate diabetic atherosclerosis in experimental settings. In clinical samples, elevated plasma lactate levels and the activation of the GPR132-Src pathway in peripheral blood mononuclear cells (PBMCs) are positively associated with coronary stenosis. These findings propose a potential mechanism through which diabetes accelerates atherosclerosis via the lactate-GPR132-Src pathway, underscoring macrophage senescence as a pivotal target in the context of diabetic atherosclerosis."

Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Metabolic Disorders • GPR132

Molecular docking investigating methotrexate as a potential target for addressing cardiovascular disease risk associated with cancer. (ASCO 2025) - " The molecular docking modeling and analysis was performed using AutoDock Tool 4.2 version software to model the binding interaction between RAGE and each of the four anticancer drugs studied: MTX, Niraparib, Abemaciclib, and Saracatinib. The molecular docking findings show that among the anticancer drug interactions studied, MTX had the strongest binding interaction with RAGE. This suggests that MTX may potentially reduce the progression of atherosclerosis and CVD risk among cancer survivors by inhibiting RAGE."

Atherosclerosis • Cardiovascular • Oncology

The Effects of Neuronal Fyn Knockdown in the Hippocampus in the Rat Kainate Model of Temporal Lobe Epilepsy. (PubMed, Cells) - "Persistent neuronal loss, astrogliosis, and microgliosis suggested limited effectiveness of neuronal-specific fyn knockdown at this timepoint. An extended-duration fyn knockdown study, or using broad SFK inhibitors such as saracatinib or tau-SH3 blocking peptides, may effectively prevent SE-induced epileptogenesis."

Journal • Preclinical • CNS Disorders • Epilepsy • Inflammation • DLG4

CT7439 an oral first-in class selective CDK12 and 13 inhibitor and cyclin K degrader: Profiling activity and combination efficacy in an ovarian cancer model (AACR 2025) - "CT7439 activity in OV-90 in cellular assays:OV-90GrowthCCNK**BRAC1*ERCC4*RAD51C*POLQ*MCL-1*IC50 nM (SD)4.40.66 (0.1)1.7 (0.4)0.82(0.3)1.2 (0.7)1.9(0.2)>20Data is mean ± SD (**Western blot, *qPCR) In addition to single agent activity of CT7439 a strong combination activity between CT7439 and the PARP inhibitors Olaparib, Niraparib and AZD10530 as well as the carboplatin was observed in an OV-90 cellular confluency assay. CT7439 is an orally bioavailable selective CDK12/13 inhibitor and degrader of CCNK. Pre-clinical studies demonstrates clinical potential for monotherapy use in solid tumors and as a combination therapy with agents known to cause a DNA damage response."

Clinical • Preclinical • Oncology • Ovarian Cancer • Solid Tumor • BRCA1 • CDK12 • CDK13 • ERCC4 • MCL1 • POLQ • RAD51C

Selective inhibition of stromal mechanosensing suppresses cardiac fibrosis. (PubMed, Nature) - "Pharmacological inhibition of SRC by saracatinib, coupled with TGFβ suppression, induces synergistic repression of key profibrotic gene programs in fibroblasts, characterized by a marked inhibition of the MRTF-SRF pathway, which is not seen after treatment with either drug alone. Importantly, the dual treatment alleviates contractile dysfunction in fibrotic engineered heart tissues and in a mouse model of heart failure. Our findings point to joint inhibition of SRC-mediated stromal mechanosensing and TGFβ signalling as a potential mechanotherapeutic strategy for treating cardiovascular fibrosis."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology

Advancements in mechanisms and drug treatments for fibrodysplasia ossificans progressiva. (PubMed, J Zhejiang Univ Sci B) - "Currently, researchers are intensively studying the pathogenesis of FOP at various stages and developing promising drug candidates, including saracatinib, palovarotene, and rapamycin. This review provides an overview of progress in understanding the mechanism of FOP and the development of therapeutic drugs, with the goal of providing insights for further research and the development of new treatment methods."

Journal • Review • Genetic Disorders • ACVR1

High-throughput screening identifies bazedoxifene as a potential therapeutic for dysferlin-deficient limb girdle muscular dystrophy. (PubMed, Br J Pharmacol) - "Our drug screening identified saracatinib and bazedoxifene as potential treatments for LGMD R2, especially for patients with the L1341P mutation. The widespread protective effect of bazedoxifene reveals a new avenue toward genotype-independent treatment of LGMD R2 patients."

Journal • Genetic Disorders • Muscular Dystrophy

The IGF2BP1 oncogene is a druggable m6A-dependent enhancer of YAP1-driven gene expression in ovarian cancer. (PubMed, NAR Cancer) - "In contrast, SRC inhibition with Saracatinib fails to inhibit YAP1/TAZ-driven transcription and cell growth in general...In such invasive carcinoma models, the combined inhibition of SRC, IGF2BP1, and YAP1/TAZ proved superior over monotherapies. These findings highlight the therapeutic potential of targeting IGF2BP1, a key regulator of oncogenic transcription networks."

Journal • Oncology • Ovarian Cancer • Solid Tumor • IGF2 • IGF2BP1 • YAP1

Inhibition of Src signaling induces autophagic killing of Toxoplasma gondii via PTEN-mediated deactivation of Akt. (PubMed, PLoS Pathog) - "Saracatinib treatment in mice with pre-established cerebral and ocular toxoplasmosis promoted PTEN recruitment around tachyzoites in neural tissue impairing recruitment of activated Akt, profoundly reducing parasite load and neural histopathology that were dependent of the autophagy protein, Beclin 1. Our studies uncovered an EGFR-independent pathway activated by T. gondii that enables its survival and is central to the development of neural toxoplasmosis."

Journal • Infectious Disease • BECN1 • LAMP1 • PTEN

IGF2BP3 Triggers STAT3 Pathway by Stabilizing SRC RNA in an m6A-Dependent Manner to Promote Lymphatic Metastasis in LUAD. (PubMed, Cancer Sci) - "The cell migration and EMT function of IGF2BP3 were partially rescued by utilizing SRC siRNA or AZD0530, an SRC inhibitor. This study demonstrated that IGF2BP3 promotes lymphatic metastasis in LUAD via activating the m6A-SRC-STAT3-VEGFC signaling axis, indicating that IGF2BP3 is a potential therapeutic target to overcome metastasis in LUAD patients."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IGF2BP3 • VEGFC

A Novel Prognostic Risk Model Based on Oxidative Stress to Predict Survival and Improve Treatment Strategies in Stomach Adenocarcinoma. (PubMed, Comb Chem High Throughput Screen) - "Our study has effectively established an oxidative stress-related prognostic model, providing a promising tool for personalized clinical strategies and improved STAD patient outcomes."

IO biomarker • Journal • Gastric Adenocarcinoma • Gastric Cancer • Oncology • Solid Tumor • ADCYAP1 • ANXA5 • CD36 • NOS3 • SCARB1 • SERPINE1

Drug Development. (PubMed, Alzheimers Dement) - "We have successfully evaluated previously reported inhibitors and introduced a novel type II Lyn kinase inhibitor with picomolar (pM) activities suitable for use as chemical probes to investigate the role of Lyn in TREM2-mediated microglial activation."

Journal • Alzheimer's Disease • CNS Disorders • LYN

A Pharmacokinetic and Randomized Trial of Neoadjuvant Treatment With Anastrozole Plus AZD0530 in Postmenopausal Patients With Hormone Receptor Positive Breast Cancer (clinicaltrials.gov) - P1/2 | N=71 | Completed | Sponsor: Joyce Marie Slingerland, MD | Phase classification: P2 ➔ P1/2

Phase classification • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Mesothelin Promotes Acute Myeloid Leukemia Cell Proliferation, Adhesion, and Chemoresistance through Novel Binding Partner Lyn (ASH 2024) - "To investigate the role of Lyn in MSLN-induced resistance to Ara-C, we used saracatinib (pan-SFK inhibitor) and bafetinib (Lyn inhibitor) in conjunction with Ara-C. Taken together, our data support MSLN playing an oncogenic role through increased proliferation, cell cycle progression, metabolic fitness, ECM adhesion, and Ara-C resistance. We identified a novel MSLN-Lyn signaling axis that could be used to improve targeted therapy approaches."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • LYN • MSLN • MUC16

Exploration on the construction of a bladder cancer prognostic model based on disulfidptosis-related lncRNAs and its clinical significance. (PubMed, Sci Rep) - "Lastly, the drug sensitivity analysis revealed that the BLCA cells in the high-risk group showed an increased sensitivity to cisplatin, sunitinib, cetuximab, axitinib, docetaxel, saracatinib, vinblastine and pazopanib compared with those in the low-risk group. According to the Quantitative real time PCR results, we found that five lncRNAs of the risk model were more highly expressed in BCa cell lines than human immortalized uroepithelial cell line. The disulfidptosis-related lncRNA risk model has a valuable effect in assessing the prognosis of BLCA patients."

Biomarker • IO biomarker • Journal • Tumor mutational burden • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • TMB

A Multi-Omics Prognostic Model Capturing Tumor Stemness and the Immune Microenvironment in Clear Cell Renal Cell Carcinoma. (PubMed, Biomedicines) - "The CRCS2 subtype was in a hypoxic state and was characterized by suppression and exclusion of immune function, which was sensitive to gefitinib, erlotinib, and saracatinib. Our findings highlight the key role of CSCs in shaping the ccRCC tumor microenvironment, crucial for therapy research and clinical guidance. Recognizing tumor stemness helps to predict treatment efficacy, recurrence, and drug resistance, informing treatment strategies and enhancing ccRCC patient outcomes."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • SAA2

Validation of a functional human AD model with four AD therapeutics utilizing patterned ipsc-derived cortical neurons integrated with microelectrode arrays. (PubMed, Sci Rep) - "LTP was induced by tetanic electrical stimulation, and LTP maintenance was significantly reduced in the presence of Amyloid-Beta 42 (Aβ42) oligomers compared to the controls, however, co-treatment with AD therapeutics (Donepezil, Memantine, Rolipram and Saracatinib) corrected Aβ42-induced LTP impairment. The results illustrate the utility of the system as a validated platform to model MCI AD pathology, and potentially for the pre-MCI phase before significant neuronal death. This system also has the potential to become an ideal platform for high-content therapeutic screening for other neurodegenerative diseases."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Aβ42

Histones in extracellular vesicles amplify NLRP3-inflammasome activation and alpha-synuclein aggregation in environmentally linked Parkinson's disease (Neuroscience 2024) - "The Fyn inhibitor saracatinib, or Fyn knockdown, dampened H3-mediated NLRP3 inflammasome activation, suggesting the involvement of Fyn kinase in this process. Interestingly, we found rH3 interacted with monomeric α-syn, augmenting its aggregation, suggesting that H3 can serve as a possible co-factor regulating the pathogenic α-syn protein misfolding process. Collectively, these results demonstrate that H3 in EVs may serve as a key pro-inflammatory amplifier of α-syn protein aggregation and neuroinflammation through the activation of NLRP3 inflammasome signaling via Fyn kinase signaling."

Late-breaking abstract • CNS Disorders • Parkinson's Disease • IL18 • IL1B • NLRP3

Gender-different effect of Src family kinases antagonism on photophobia and trigeminal ganglion activity. (PubMed, J Headache Pain) - "In conclusion, our data revealed that SFKs antagonism reduced photophobia processing in male mice and exhibited gender-different modulation of trigeminal ganglion activity, primarily manifesting as alterations in the transcriptome profile. These findings underscore the potential of SFKs antagonism for allieving photophobia in males, highlighting its value in the emerging field of precision medicine."

Journal • CNS Disorders • Migraine • Pain • ADCYAP1 • AKT1 • CREBBP • SCN8A • TRPA1 • TRPM3 • ZMYND8

Enhanced Fyn-tau and NR2B-PSD95 interactions in epileptic foci in experimental models and human epilepsy. (PubMed, Brain Commun) - "The reduction of Fyn-tau and NR2B-PSD95 interactions in the saracatinib-treated group, in contrast to the vehicle-treated group, correlated with the modification in seizure progression in the rat chronic epilepsy model. These findings from animal models and human epilepsy provide evidence for the role of Fyn-tau and NR2B-PSD95 interactions in seizure-induced brain pathology and suggest that blocking such interactions could modify the progression of epilepsy."

Journal • Alzheimer's Disease • CNS Disorders • Epilepsy • DLG4

Construction of a prognostic model for colon cancer by combining endoplasmic reticulum stress responsive genes. (PubMed, J Proteomics) - "Finally, based on the cMAP database, we identified several potential drugs that could target high-risk groups, such as Dasatinib, GNF-2, Saracatinib, and WZ-1-84. This model can be used as a predictor of prognosis and immunotherapy response in colon cancer patients. At the same time, model-based prediction of drugs can also be a potential option for colon cancer treatment in the future."

IO biomarker • Journal • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • EIF4A1 • GRIN2B • IRX3 • LRRC59 • NTRK2 • XBP1

Follow-up STOPFOP: A Phase II Clinical Trial to Prevent Heterotopic Ossification in FOP Using Saracatinib (AZD0530) (ASBMR 2024) - No abstract available

Clinical • P2 data • Growth Hormone Deficiency (Adult) • Orthopedics