saracatinib (AZD0530) / AstraZeneca - LARVOL DELTA

Current review on inducible nitric oxide synthase and Src tyrosine kinase inhibitors as disease-modifiers in preclinical models of epilepsy. (PubMed, Histol Histopathol) - "While the current standard of care can alleviate symptoms and reduce mortality, they do not address long-term neurological consequences. In this review, we discuss preclinical testing of two CNS-targeted drugs, iNOS and SFK inhibitors 1400W and Saracatinib (SAR; AZD0530), respectively, as potential disease-modifiers."

Journal • Preclinical • Review • CNS Disorders • Epilepsy • Inflammation • Pain

THY1 Mediates Treatment Resistance in H3K7M Pediatric Tumors and is Therapeutically Targetable (SNO 2025) - "We have uncovered that the Thy1-Fyn signaling cascade mediates rapid DNA repair and treatment resistance. Pharmacological Fyn inhibition successfully delays DNA repair which could improve patient survival. As saracatinib is highly brain penetrant(0.5:1 Brain: Plasma ratio) and has demonstrated safety in Phase I/II Alzheimer's clinical trials, it is an ideal drug for clinical translation."

Clinical • Alzheimer's Disease • Brain Cancer • CNS Disorders • Diffuse Midline Glioma • Glioma • Oncology • Pediatrics • Solid Tumor • THY1

Saracatinib Promotes Hippocampal Myelin Regeneration and Oligodendrocyte Precursor Cell Maturation by Inhibiting the NOTCH1 Signaling Pathway in Epileptic Mice. (PubMed, Neurochem Res) - No abstract available

Journal • Preclinical • CNS Disorders • Epilepsy • Solid Tumor • NOTCH1

Chronic alcohol intake elicits distinct multi-omic profiles in the liver versus skeletal muscle of mice. (PubMed, bioRxiv) - "Finally, computational drug repurposing identified several compounds for therapeutic targeting of alcohol-induced liver (e.g., saracatinib, GSK126) and muscle (e.g., metformin, trichostatin A) pathophysiology, perhaps working partly to counter metabolic dysregulation. Overall, our study provides a tractable list of therapeutic targets and treatments to help expedite the understanding of and countermeasures against alcohol-related liver disease and alcohol-related myopathy in humans."

Journal • Preclinical • Hepatology • Metabolic Disorders • Myositis

THY1 Mediates Treatment Resistance in H3K7M Pediatric Tumors and is Therapeutically Targetable (WFNOS 2025) - "We have uncovered that the Thy1-Fyn signaling cascade mediates rapid DNA repair and treatment resistance. Pharmacological Fyn inhibition successfully delays DNA repair which could improve patient survival. As saracatinib is highly brain penetrant(0.5:1 Brain: Plasma ratio) and has demonstrated safety in Phase I/II Alzheimer’s clinical trials, it is an ideal drug for clinical translation."

Clinical • Alzheimer's Disease • Brain Cancer • CNS Disorders • Diffuse Midline Glioma • Glioma • Oncology • Pediatrics • Solid Tumor • THY1

The Brain's SOS, A Systems Approach to Neuroinflammation, Seizures, and Recovery post-soman Exposure (Neuroscience 2025) - "Saracatinib effectively disrupted the injury cascade, promoting recovery and preserving neural function. This study provides critical insights into the neurobiological mechanisms of soman-induced brain injury and suggests novel opportunities for neuroprotective strategies to mitigate long-term neurological sequelae."

CNS Disorders • Epilepsy • Vascular Neurology

Novel Orally Available Degrader to Target Lck in T-Cell Acute Lymphoblastic Leukemia (ASH 2023) - "In comparison to the LCK inhibitors dasatinib (~0.307 nM) and saracatinib (~17.41 nM), UBX-363 (~0.121 nM) demonstrated slightly superior anti-proliferative efficacy in HSB-2 cells. These results highlight UBX-363 as a promising therapeutic agent for LCK-activated T-ALL. In the future, we will conduct additional research to explore the advantages of this degrader, such as its ability to disrupt scaffolding of LCK, over LCK small molecule inhibitors."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • Targeted Protein Degradation • T-cell Acute Lymphoblastic Lymphoma

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

Src and Abl as Therapeutic Targets in Lung Cancer: Opportunities for Drug Repurposing. (PubMed, Pharmaceuticals (Basel)) - "This review aims to provide a comprehensive overview of five tyrosine kinase inhibitors-saracatinib, imatinib, PP2, nilotinib and, tirbanibulin-that act on Src and/or Abl. Although clinical data for these drugs in lung cancer remain limited, preclinical and clinical studies suggest promising therapeutic potential, particularly in specific molecular subtypes. Overall, this review highlights the therapeutic potential of Src and Abl inhibitors beyond their original contexts and supports their possible role in lung cancer therapy, considering the disease's high heterogeneity and the growing applicability of personalized medicine."

Journal • Review • Lung Cancer • Oncology • Solid Tumor

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL EVALUATING THE SAFETY, TOLERABILITY, AND PHARMACODYNAMICS OF SARACATINIB IN IDIOPATHIC PULMONARY FIBROSIS (CHEST 2025) - "Background therapy with nintedanib or pirfenidone was not permitted. Among adult patients with IPF, saracatinib demonstrated acceptable safety and PD profiles but did not significantly change the decline in FVC, DLCO, HRCT estimation of the degree of fibrosis, or QOL compared to controls. CLINICAL IMPLICATIONS: In this 24 week trial, treatment with saracatinib did not slow the rate of decline in FVC compared to controls. Interestingly, the rate of decline in FVC for both the saracatinib and placebo groups was substantially lower than in other recent clinical trials in IPF."

Clinical • Late-breaking abstract • PK/PD data • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases

The NADPH Oxidase DUOX1 Contributes to Profibrotic Macrophage Activation and Pulmonary Fibrosis. (PubMed, Am J Respir Cell Mol Biol) - "Finally, these DUOX1-mediated actions were associated with oxidative activation of Src kinase via cysteine oxidation, and were inhibitable by saracatinib, a clinically used Src inhibitor. Collectively, our findings highlight the involvement of DUOX1 in macrophage-(myo)fibroblast crosstalk in the pathogenesis and/or progression of pulmonary fibrosis, implicating it as a putatively novel therapeutically targetable feature of this devastating disease."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • EGFR

Saracatinib Delays the Progression of Renal Interstitial Fibrosis by Inhibiting the Wnt/β-Catenin Pathway. (PubMed, Kidney360) - "This study suggests that saracatinib may be a novel therapeutic strategy for CKD treatment."

Journal • Fibrosis • Immunology • CST3

SRC Activation Drives Acquired Pemetrexed Resistance in Non-Small Cell Lung Cancer and Is Targetable by Dasatinib (IASLC-WCLC 2025) - "SRC was abrogated using both transient and doxycycline-inducible CRISPR/Cas9 systems to evaluate its role in cell viability and survival signaling. We assessed the efficacy of three SRC inhibitors—dasatinib, bosutinib, and saracatinib—using cell viability assays, colony formation assays, apoptosis detection, and cell cycle analyses...Targeting SRC, particularly with dasatinib, effectively impairs the survival of pemetrexed-resistant cells by promoting DNA damage, apoptosis, and cell cycle arrest. These findings provide a strong rationale for further preclinical and clinical investigation of SRC inhibitors, either as monotherapy or in combination with pemetrexed, as a therapeutic strategy to overcome resistance in NSCLC patients."

Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CASP3 • STAT3

STOPFOP: A Phase II Clinical Trial to Prevent Heterotopic Ossification in FOP Using Saracatinib (AZD0530) (ASBMR 2025) - P2 | No abstract available

Clinical • P2 data

STOPFOP: A Phase II Clinical Trial to Prevent Heterotopic Ossification in FOP Using Saracatinib (AZD0530) (ASBMR 2025) - P2 | No abstract available

Clinical • P2 data

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

Mitigating organophosphate nerve agent, soman (GD), induced long-term neurotoxicity: Saracatinib, a Src Tyrosine Kinase inhibitor, as a potential countermeasure. (PubMed, J Neuroinflammation) - "Long-term SAR treatment revealed disease-modifying effects by protecting the brain from soman induced neuroinflammation and neurodegeneration, while also reducing severity of spontaneous seizures. Furthermore, SAR mitigated some soman induced behavioral impairments and brain MRI. These findings highlight the therapeutic potential of Src tyrosine kinase inhibition in soman-induced chronic neurotoxicity."

Journal • CNS Disorders • Cognitive Disorders • Epilepsy • Inflammation • Mood Disorders • Pain • Psychiatry

Autophagy suppression via SRC induction represents a therapeutic vulnerability for BAP1-mutant cancers. (PubMed, Autophagy) - "Treatment of these cells with SRC inhibitors (such as dasatinib, bosutinib and saracatinib) and autophagy-inducing drugs (such as Tat-BECN1, SW076956 and SW063058) demonstrated a synergistic interaction between these compounds both in vitro and in ovo using a chick Chorioallantoic Membrane (CAM) assay. Our findings elucidate a novel BAP1-SRC-BECN1-autophagy regulatory axis that can be exploited therapeutically in precision oncology through the combination of SRC inhibitors and autophagy inducers, contingent upon patient stratification for BAP1 loss.Significance: Deadly cancers with BAP1 mutations suppress autophagy by phosphorylating the autophagy regulator BECN1 via the proto-oncogene SRC. Treatment with SRC inhibitors and autophagy inducers exhibited synergism in vitro, in ovo and in patient-derived tumor organoids with BAP1 loss, paving the way for treating BAP1-deficient cancers with autophagy inducers and kinase inhibitors."

Journal • Biliary Cancer • Cholangiocarcinoma • Clear Cell Renal Cell Carcinoma • Eye Cancer • Genito-urinary Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BAP1 • BECN1

Mitigating Organophosphate Nerve Agent, Soman (GD)-Induced Long-Term Neurotoxicity: Saracatinib, a Src Tyrosine Kinase Inhibitor, as a Potential Countermeasure. (PubMed, Res Sq) - "Seizure severity was quantified for an hour before administering midazolam (3 mg/kg, i.m.). Furthermore, it provided partial protection against behavioral impairments and MRI deficits in the short term. These findings highlight the therapeutic potential of Src tyrosine kinase inhibition in addressing chronic neurotoxicity induced by soman."

Journal • CNS Disorders • Epilepsy • Inflammation • Mood Disorders • Pain • Psychiatry

Prognostic and tumor microenvironmental features of gastric cancer revealed by macrophage polarization and protein lactylation-related genes. (PubMed, Front Genet) - "Drug sensitivity analysis highlighted AZD.0530, CCT007093, DMOG, JNJ.26854165, and LFM.A13 as promising therapeutic candidates. In both datasets, expression of prognostic genes was significantly higher in the GC cohort. This study identified ERCC6L and MYB as key prognostic genes, facilitating the development of a risk model that offers novel insights into potential therapeutic strategies for GC."

Biomarker • Journal • Gastric Cancer • Oncology • Solid Tumor • ERCC6 • MUC16 • TP53 • TTN

Fyn kinase mediates the development of rats with chronic obstructive pulmonary disease by modulating the activation of p38 MAPK and NF-κB. (PubMed, Iran J Basic Med Sci) - "Subsequently, the rats were treated with the Fyn-specific inhibitor AZD0530...Collectively, these data show that Fyn promotes COPD development by modulating the p38 MAPK and NF-κB signaling pathways. Fyn might be a promising therapeutic target for COPD."

Journal • Preclinical • Chronic Obstructive Pulmonary Disease • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases • CD68 • IL6 • TNFA

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