saracatinib (AZD0530) / AstraZeneca - LARVOL DELTA

Mechanotransduction-driven macrophage polarization via Integrin-SRC-STAT6 pathway in distraction osteogenesis. (PubMed, J Orthop Translat) - "In vivo, Saracatinib and TGF-β were administered locally in DO models...These findings reveal a novel mechano-immune regulatory axis that supports bone regeneration in DO. This research confirms the core concept of "mechano-immunoregulation" and identifies actionable therapeutic targets, enabling the development of targeted therapies for refractory bone defects by modulating the integrin-β1/SRC/STAT6 pathway and TGF-β1 to enhance bone regeneration."

Journal • Musculoskeletal Diseases • Orthopedics • IL10 • TGFB1

Transcriptomic signatures of IPF in ALI-cultured airway cells and their therapeutic implications. (PubMed, Thorax) - "This study defines epithelial-mesenchymal programmes of the airway mucosa at an early, diagnostic stage of IPF and demonstrates distinct drug responses at single-cell resolution. By linking airway-derived phenotypes to antifibrotic efficacy, our findings highlight the therapeutic potential of saracatinib and may inform future treatment strategies."

Journal • Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • KRT5 • PDGFRA • SPP1 • TGFB1 • TP63

A hydrophilic interaction UPLC-MS/MS quantitative method for the quantification of saracatinib in the human liver microsome matrix and its application in in vitro metabolic stability assessment. (PubMed, Anal Methods) - "SRB and baricitinib, used as an internal standard (IS), were isolated from HLMs using protein precipitation with acetonitrile (ACN) as the extracting agent. The metabolic stability parameters, including the in vitro half-life (t1/2) and intrinsic clearance (Clint) of SRB, were assessed at 17.24 min and 47.02 mL min-1 kg-1, respectively. In silico research indicated that slight structural modifications to the N-methyl piperazine ring in the drug design may enhance metabolic stability and safety compared with those of SRB."

Journal • Preclinical • ABL1 • BCR

Fyn-Saracatinib Complex Structure Reveals an Active State-like Conformation. (PubMed, Int J Mol Sci) - "SPR single-cycle kinetics shows that saracatinib binds the isolated Fyn KD and full-length Fyn with low-nanomolar affinity, whereas dasatinib binds with subnanomolar affinity and markedly slower dissociation. Comparison with reported saracatinib-bound structures of other kinases suggests that the active-state geometry observed for Fyn creates a pocket not observed in inactive-like complexes, providing a structural handle for designing Fyn-selective inhibitors. Comparison with all saracatinib-bound kinase co-structures currently available in the PDB (ALK2 and PKMYT1) indicates a conserved monodentate hinge binding mode but kinase-dependent αC-helix conformations, providing a structural rationale for designing Fyn-selective analogues."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • HCK • PKMYT1

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

CXCL11 levels regulate lung Treg responses to deter the onset of HIV-related COPD. (PubMed, Respir Res) - "These findings indicate that cigarette smoke activates c-Src to suppress CXCL11 levels thereby diminishing lung Treg responses that counter airways disease and lung tissue destruction in HIV-infected individuals."

Journal • Chronic Obstructive Pulmonary Disease • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • CXCL11 • ELANE

A new oxidative stress-related lncRNA signature predicts the prognosis of colorectal cancer patients. (PubMed, Discov Oncol) - "High-risk patients were found to be more sensitive to treatment drugs ABT.263, AZD.0530, gefitinib, imatinib, PAC.1, and shikonin. The predictive model we constructed can independently predict the prognosis of patients with CRC. Further experimental validation and mechanistic studies are warranted to elucidate the precise role of OS-related lncRNAs in CRC pathogenesis."

Journal • Colorectal Cancer • Oncology • Solid Tumor • SNHG16

Comparative multi-omics in female mice reveals tissue-specific vulnerabilities to chronic alcohol intake. (PubMed, Alcohol Clin Exp Res (Hoboken)) - "Overall, this study provides a list of therapeutic targets and treatments to help expedite the understanding of and countermeasures against ALD and myopathy in humans."

Clinical • Journal • Preclinical • Hepatology • Myositis

Dual targeting of iNOS and Src tyrosine kinase as a superior therapeutic strategy against soman-induced long-term neurotoxicity: multimodal biomarker, imaging, and neurobehavioral outcome analyses. (PubMed, Acta Neuropathol Commun) - No abstract available

Biomarker • Journal • CNS Disorders • Epilepsy

STL1267 Inhibits Myofibroblast Differentiation in a TGFβ1-Driven Human Lung Fibroblast Model. (PubMed, Am J Physiol Cell Physiol) - "Comparative studies with other Rev-erbα agonists (GSK4112, SR9009), Saracatinib, and FDA-approved antifibrotic drugs (Pirfenidone, Nintedanib) demonstrated superior efficacy of STL1267 in inhibiting both preventive and post-fibrotic induction models. These findings highlight Rev-erbα as a key regulator of myofibroblast differentiation and support both STL1267 and GSK4112 as promising candidates for circadian-based antifibrotic therapy. Future in vivo studies are warranted to evaluate its translational potential in idiopathic pulmonary fibrosis."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Inflammation • Interstitial Lung Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • COL1A1 • IL10 • IL13 • IL4 • NR1D1 • TGFB1

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