saracatinib (AZD0530) / AstraZeneca - LARVOL DELTA

Single-cell profiling of diagnostic-stage IPF airway mucosa reveals saracatinib as a potent modulator of epithelial and mesenchymal programs (ERS 2026) - "We further assessed transcriptional and functional responses to the antifibrotic drugs nintedanib and pirfenidone, as well as the Src kinase inhibitor saracatinib. Although all three treatments attenuated IPF-associated transcriptional programs, saracatinib most effectively suppressed fibroblast activation and epithelial proliferation. Together, these findings define epithelial–mesenchymal programs of the airway at the diagnostic stage of IPF and highlight saracatinib's relevance for future therapeutic strategies."

Idiopathic Pulmonary Fibrosis • Immunology • KRT5 • PDGFRA • SPP1 • TGFB1 • TP63

STOPFOP: Saracatinib Trial TO Prevent FOP (clinicaltrials.gov) - P2 | N=20 | Active, not recruiting | Sponsor: Amsterdam UMC, location VUmc | Recruiting ➔ Active, not recruiting | Trial completion date: May 2025 ➔ Nov 2026 | Trial primary completion date: May 2025 ➔ Nov 2025

Enrollment closed • Trial completion date • Trial primary completion date

Targeting treatment resistance in H3K27M pediatric tumors (EANO 2026) - "We have uncovered that the Thy1-Fyn signaling cascade mediates rapid DNA repair and radiation resistance. Pharmacological Fyn inhibition successfully delays DNA repair in vitro and in vivo, radiosensitizes tumors, and significantly improves survival of mouse models. 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 • Brain Cancer • Diffuse Midline Glioma • Glioma • Oncology • Solid Tumor • HRD • THY1

Low concentrations of saracatinib promote definitive endoderm differentiation through inhibition of FAK-YAP signaling axis (TTS 2026) - "This mechanism has the potential to optimize DE differentiation protocols and reduce the need for AA. Our findings expand the significance of FAK in developmental biology and regenerative medicine, providing a better foundation for enhancing the functionality of islet organoids."

PDX1

Rosmarinic Acid Alleviates Cisplatin-Induced Acute Kidney Injury by Targeting FYN to Regulate Ferroptosis. (PubMed, Food Sci Nutr) - "Cisplatin (CDDP) is a widely used chemotherapeutic agent, but its nephrotoxic side effects limit its clinical application, which can lead to severe acute kidney injury (AKI). Additionally, pharmacological inhibition of FYN using Saracatinib in vivo or genetic knockdown of FYN in HK-2 cells effectively alleviated CDDP-induced renal tubular injury and lipid metabolic dysregulation. In conclusion, our findings indicate that RA alleviates CDDP-AKI by targeting FYN to regulate the ferroptosis pathway, highlighting that RA is a promising candidate for preventing and treating CDDP-AKI."

Journal • Acute Kidney Injury • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • GPX4

Host immune network-guided reverse vaccinology approach for prioritizing candidate antigens in Schistosoma japonicum-associated liver fibrosis. (PubMed, PLoS Negl Trop Dis) - "This difference may suggest a distinct predicted binding mode rather than Saracatinib-like kinase inhibition. Overall, the vaccine-screening profile and predicted FYN-associated interaction may provide a computational rationale for further experimental evaluation of DRE2_SCHJA as a candidate antigen in the immune-fibrotic context of SSLF."

Journal • Fibrosis • Immunology • Infectious Disease • Liver Cirrhosis • BCL2

STOPFOP: A Phase II Clinical Trial to Prevent Heterotopic Ossification in FOP Using Saracatinib (AZD0530) (ASBMR 2026) - No abstract available

Clinical • P2 data

Comparison of different SYK-inhibitors in platelet-rich plasma (ISTH 2026) - "Methods Platelet-rich plasma (PRP) from healthy donors (n=3; technical duplicates) was incubated with SYK inhibitors (Sovleplenib, P505-15, R406, BI2494) at 100 µM-100 nM...Saracatinib (pan-Src-family kinase inhibitor) and Pirtobrutinib (BTK inhibitor) served as comparators...These findings provide a baseline reference for subsequent studies in CKD patient samples to define how CKD- associated inflammation modifies SYK-dependent platelet responses. Table or Figure Upload (1) Page 2 DOI*10.1016/j.rpth.2026.105268"

Cardiovascular • Chronic Kidney Disease • Hematological Disorders • Inflammation • Nephrology • Renal Disease • Thrombosis • SYK

Dysregulated glucocorticoid-responsive immune genes in peripheral blood mononuclear cells as a shared molecular signature of autism spectrum disorder and irritable bowel syndrome. (PubMed, PLoS One) - "These findings define a shared GRI-associated molecular signature linking systemic stress adaptation to immune dysregulation along the brain-gut axis. This study provides novel mechanistic insights and identifies potential transcriptomic biomarkers and therapeutic targets addressing the shared molecular architecture between ASD and IBS."

Journal • Autism Spectrum Disorder • Gastrointestinal Disorder • Genetic Disorders

LD-associated signatures identified by perilipin-based proximity labeling proteomics reveal GNA14 as a therapeutic and prognostic target in renal cell carcinoma. (PubMed, Cancer Gene Ther) - "Drug sensitivity analysis suggested differential responses to Sorafenib, Cediranib, and Saracatinib...Excitingly, lovastatin can partially block the detrimental pathway by which GNA14 promotes lipid accumulation. Therefore, combining lovastatin with GNA14 overexpression yields a more effective suppression of RCC."

Journal • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Metabolic Disorders • Oncology • Renal Cell Carcinoma • Solid Tumor • PLIN2

Comprehensive Pan-Cancer Bioinformatics Analysis Identifies DHX58 as a Promising Therapeutic Target and Prognostic Biomarker Across Multiple Tumor Types. (PubMed, Asian Pac J Cancer Prev) - "Our pan-cancer analysis reveals that DHX58 has context-specific prognostic and predictive roles. While discrepancies between platforms exist, DHX58 emerges as a potential biomarker in specific cancers, particularly in the context of therapies involving agents like birinapant. These findings warrant further mechanistic and clinical investigation."

Biomarker • Journal • Pan tumor • Colon Adenocarcinoma • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A SIRT1-stabilizing nanofibrous platform via suppression of ubiquitination for enhanced diabetic wound healing: synergistic therapy with saracatinib and MOF-818. (PubMed, J Nanobiotechnology) - "Comprehensive evaluations of mechanical properties, Cu/Zr biodistribution, and serum biochemistry supported the structural applicability and favorable preliminary biosafety of the platform. Collectively, P-GMOF-818@Sec represents a pathophysiology-guided therapeutic strategy that uniquely integrates extracellular microenvironment regulation with intracellular stabilization of a key cytoprotective protein, SIRT1, for enhanced diabetic wound healing."

Journal • Infectious Disease • Inflammation • Targeted Protein Degradation • FOXO3 • SIRT1 • SOD2

ET1/ETAR/NOX signaling enhances invadopodia formation, thereby promoting cell invasion in gallbladder cancer cells (EACR 2026) - "This question is addressed in the present study.Material and The GBC cell line NOZ was treated with ET1 and/or Ambrisentan (ETAR antagonist), and/or Diphenyleneiodonium (pan-NOX proteins inhibitor), and/or Saracatinib (Src phosphorylation inhibitor). ET1/ETAR signaling promotes an increase in NOX-dependent ROS production, which is associated with increased invasiveness of GBC cells through enhanced invadopodia formation."

Gallbladder Cancer • Oncology • Solid Tumor • EDN1

Development of an AQbD-guided sustainable RP-HPLC method for simultaneous quantification of saracatinib and rapamycin in lipid-polymer hybrid nanocarriers. (PubMed, RSC Adv) - "Environmental sustainability was assessed using complementary green analytical metrics, including AGREE (0.68), AGREEprep (0.63), and ComplexMoGAPI (81), indicating a favourable sustainability profile with moderate-to-high environmental compatibility. Overall, the study delivers a validated, regulatory-compliant, and moderately green RP-HPLC method for the simultaneous quantification of dual-drugs, supporting the advancement of nanocarrier-based combination therapies in HNC management."

Journal • Head and Neck Cancer • Oncology • Solid Tumor

Disrupting oncogenic signaling in triple negative breast cancer: The interplay of Cx43, Pyk2, and Src in MDA-MB-231 cells. (PubMed, Cell Tissue Res) - "In MDA-MB-231 cells, the Pyk2 inhibitor PF4618433 and Src inhibitor Saracatinib modestly reduced metabolic activity at high concentrations; however dual treatment produced a dose-dependent and synergistic reduction in viability...Dual treatment did not further decrease these signaling nodes but nonetheless produced stronger functional inhibition of viability and motility, and the shared regulation of p-Erk1/2 by Pyk2 and Src may help explain how compensatory Pyk2 activation limits the effectiveness of Src-targeted therapies. Together, these findings show that coordinated Pyk2 and Src inhibition restores Cx43 organization and disrupts multiple malignant traits in TNBC cells, supporting this combination as a promising therapeutic strategy."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • NOTCH1 • TAFAZZIN

VPS35 controls hepatocellular proliferation through SRC signalling and promotes diethyl nitrosamine-induced tumor initiation. (PubMed, Cell Mol Gastroenterol Hepatol) - "Our in vivo data identify murine VPS35 as a critical regulator of hepatocellular proliferation in postnatal livers, but not after PH. Although VPS35 deficiency mitigates DEN-induced liver lesion formation, it does not affect tumor progression, arguing against a role for VPS35 as a canonical oncogene."

Journal • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • STAT3

KIF18B Promotes Neuroendocrine Prostate Cancer Progression through ITGB1-Mediated Dual Suppression of YAP1 (AUA 2026) - "Rescue experiments used EZH2 inhibitor GSK126 and Src inhibitor Saracatinib...KIF18B knockdown reduced xenograft tumor volume 61%; combined with cisplatin achieved 79% inhibition versus 35% cisplatin alone... We establish a SUMOylation-KIF18B-ITGB1-EZH2/Src-YAP1 axis driving NEPC through dual YAP1 suppression. KIF18B represents a promising biomarker and therapeutic target for precision NEPC treatment."

Genito-urinary Cancer • Genitourinary Neuroendocrine Carcinoma • Oncology • Prostate Cancer • Solid Tumor • ASCL1 • CHGA • EZH2 • ITGB1 • RB1 • SYP • TP53 • YAP1

Divergent mechanisms, unified therapy: saracatinib targets Src/HIF signaling in endothelial and microglial cells to Treat retinopathy. (PubMed, Biochem Pharmacol) - "Saracatinib mitigates RNV via cell-specific regulation of the Src-HIF axis: targeting HIF-1α in ECs to inhibit angiogenesis and HIF-1α/HIF-2α in microglia to alleviate inflammation. It addresses inflammation-angiogenesis crosstalk, offering a promising alternative or adjunct to anti-VEGF therapies."

Journal • Age-related Macular Degeneration • Inflammation • Ocular Inflammation • Ophthalmology • Retinal Disorders • EPAS1 • HIF1A • IL1B • TNFA

Upregulation of Sox2 Following Saracatinib Treatment Contributes to a Resistant Phenotype in Colorectal Cancer Cells under Growth Factor-Supplemented Conditions. (PubMed, Oncol Res) - "Wild-type and 5-fluorouracil-resistance acquired SNU-C5 colorectal cancer cells were cultured in both monolayer and spheroid systems under fetal bovine serum (FBS) or growth factor (GF) supplemented conditions. Saracatinib exerts anti-cancer effects in colorectal cancer cells by downregulating MAPKs, EGFR, and CSC-associated markers. However, paradoxical upregulation of Sox2 influenced spheroid formation under GF-supplemented conditions, suggesting that Sox2 may contribute to drug resistance or recurrence in colorectal cancers."

Journal • Colorectal Cancer • Oncology • Solid Tumor • SOX2

LEP-AD: language embedding of proteins and attention to drugs predicts drug-target interactions. (PubMed, J Cheminform) - "In summary, our benchmark highlights the strengths and limitations of current drug-target interaction models across diverse datasets and evaluation settings. The results emphasize the impact of pretrained protein and molecular representations on predictive performance and illustrate the persistent challenges of generalization, while the modular LEP-AD framework provides a flexible reference point for comparative evaluation."

Journal

Targeting SRC enhances differentiation and promotes multifaceted cell death mechanisms in recurrent group 3 medulloblastoma. (PubMed, Cell Death Dis) - "Importantly, in a therapeutically relevant orthotopic G3 MB model, administration of the re-purposed blood-brain-barrier permeable SRC inhibitor, Saracatinib, in conjunction with CRT, significantly reduced tumor burden and improved animal survival compared to CRT treatment alone without any neurotoxic side effects. Overall, our results underscore the pivotal role of SRC in enhancing stemness and aggressive behavior in CRT-resistant recurrent G3 MB. Targeting SRC not only promotes cell death through apoptosis and necroptosis but also encourages differentiation, positioning it as a promising therapeutic target for rapid clinical interventions."

Journal • Brain Cancer • Medulloblastoma • Oncology • Solid Tumor • NANOG • NOTCH1 • POU5F1 • SOX2 • TUBB3

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

Role of Src family kinases Fyn and Lyn in arenavirus infection. (PubMed, J Virol) - "Moreover, the FDA-approved Src inhibitor saracatinib exhibits broad-spectrum efficacy, suppressing LCMV strains as well as the authentic LASV in vitro, while reducing LCMV viral loads and histopathology in vivo. These findings redefine tyrosine kinases as host targets, offering a novel host-directed antiviral strategy by repurposing existing clinical compounds."

Journal • CNS Disorders • Cytomegalovirus Infection • Infectious Disease • LYN

A phosphoproteomic LC-MS approach delineates Src-family kinase contributions to profibrotic signalling in lung fibroblasts (ERS LSC 2026) - "Here, we elaborate on a phosphoproteomic LC-MS approach to compare saracatinib and NXP900 and delineate specific contributions of the SFKs to TGF-?1-mediated profibrotic signalling. Kinase-substrate analyses comparing compounds highlighted phosphorylation of substrates downstream of AKT1/2/3, GSK3A/B, BRAF, MTOR, and PAK1/2 as differentially-regulated, while phosphorylation downstream of AURKA/B, MARK1/2, PIM1/2, and LATS1 showed agreement. Our data show differential regulation of TGF-?1-mediated SFK signalling by different mechanistic subclasses of SFK inhibition and further suggests that the SFKs may regulate TGF-?1-induced cytoskeletal organization independently of collagen synthesis."

Idiopathic Pulmonary Fibrosis • Immunology • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • AKT1 • AURKA • BRAF • CDC42 • LATS1 • PIM1

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