{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:39:33Z","timestamp":1792028373917,"version":"4.4.0"},"reference-count":82,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundo Europeu de Desenvolvimento Regional (FEDER)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]},{"name":"Faculty of Medicine, University of Porto (FMUP)","award":["IF\/00092\/2014\/CP1255\/CT0004"],"award-info":[{"award-number":["IF\/00092\/2014\/CP1255\/CT0004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Saracatinib (AZD0530) is a dual Src\/Abl inhibitor initially developed by AstraZeneca for cancer treatment; however, data from 2006 to 2024 reveal that this drug has been tested not only for cancer treatment, but also for the treatment of other diseases. Despite the promising pre-clinical results and the tolerability shown in phase I trials, where a maximum tolerated dose of 175 mg was defined, phase II clinical data demonstrated a low therapeutic action against several cancers and an elevated rate of adverse effects. Recently, pre-clinical research aimed at reducing the toxic effects and enhancing the therapeutic performance of saracatinib using nanoparticles and different pharmacological combinations has shown promising results. Concomitantly, saracatinib was repurposed to treat Alzheimer\u2019s disease, targeting Fyn. It showed great clinical results and required a lower daily dose than that defined for cancer treatment, 125 mg and 175 mg, respectively. In addition to Alzheimer\u2019s disease, this Src inhibitor has also been studied in relation to other health conditions such as pulmonary and liver fibrosis and even for analgesic and anti-allergic functions. Although saracatinib is still not approved by the Food and Drug Administration (FDA), the large number of alternative uses for saracatinib and the elevated number of pre-clinical and clinical trials performed suggest the huge potential of this drug for the treatment of different kinds of diseases.<\/jats:p>","DOI":"10.3390\/ijms25084565","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T07:44:09Z","timestamp":1713771849000},"page":"4565","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Dual Drug Repurposing: The Example of Saracatinib"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5324-8826","authenticated-orcid":false,"given":"Raquel","family":"Ramos","sequence":"first","affiliation":[{"name":"PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1283-1042","authenticated-orcid":false,"given":"Nuno","family":"Vale","sequence":"additional","affiliation":[{"name":"PerMed Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"},{"name":"CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1593\/neo.10328","article-title":"SRC: A Century of Science Brought to the Clinic","volume":"12","author":"Aleshin","year":"2010","journal-title":"Neoplasia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6465","DOI":"10.1021\/jm060434q","article-title":"N-(5-Chloro-1,3-benzodioxol-4-yl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(tetrahydro-2H-pyran-4-yloxy)quinazolin-4-amine, a Novel, Highly Selective, Orally Available, Dual-Specific c-Src\/Abl Kinase Inhibitor","volume":"49","author":"Hennequin","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"799","DOI":"10.4155\/fmc.12.29","article-title":"An update on dual Src\/Abl inhibitors","volume":"4","author":"Musumeci","year":"2012","journal-title":"Future Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Jha, V., Macchia, M., Tuccinardi, T., and Poli, G. (2020). Three-Dimensional Interactions Analysis of the Anticancer Target c-Src Kinase with Its Inhibitors. Cancers, 12.","DOI":"10.3390\/cancers12082327"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8501693","DOI":"10.1155\/2016\/8501693","article-title":"Current Research Therapeutic Strategies for Alzheimer\u2019s Disease Treatment","volume":"2016","author":"Folch","year":"2016","journal-title":"Neural Plast."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/ana.24394","article-title":"Fyn inhibition rescues established memory and synapse loss in Alzheimer mice","volume":"77","author":"Kaufman","year":"2015","journal-title":"Ann. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.neuropharm.2017.11.042","article-title":"Disease-modifying benefit of Fyn blockade persists after washout in mouse Alzheimer\u2019s model","volume":"130","author":"Smith","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s40478-020-00976-9","article-title":"Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy","volume":"8","author":"Tang","year":"2020","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.2967\/jnumed.118.223867","article-title":"In Vivo Synaptic Density Imaging with 11C-UCB-J Detects Treatment Effects of Saracatinib in a Mouse Model of Alzheimer Disease","volume":"60","author":"Toyonaga","year":"2019","journal-title":"J. Nucl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13195-015-0119-0","article-title":"A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer\u2019s disease","volume":"7","author":"Nygaard","year":"2015","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1001\/jamaneurol.2019.2050","article-title":"Effect of AZD0530 on Cerebral Metabolic Decline in Alzheimer Disease","volume":"76","author":"Nygaard","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/nbt.1990","article-title":"Comprehensive analysis of kinase inhibitor selectivity","volume":"29","author":"Davis","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.phrs.2015.01.003","article-title":"Src protein-tyrosine kinase structure, mechanism, and small molecule inhibitors","volume":"94","author":"Roskoski","year":"2015","journal-title":"Pharmacol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.drudis.2016.06.007","article-title":"Standing on the shoulders of giants: A retrospective analysis of kinase drug discovery at AstraZeneca","volume":"21","author":"Kettle","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1021\/acs.chemrestox.6b00242","article-title":"Cytochrome P450 Mediated Bioactivation of Saracatinib","volume":"29","author":"Chen","year":"2016","journal-title":"Chem. Res. Toxicol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1634\/theoncologist.2010-0408","article-title":"Current Status of Src Inhibitors in Solid Tumor Malignancies","volume":"16","author":"Puls","year":"2011","journal-title":"Oncologist"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1021\/tx9902082","article-title":"Role of Quinones in Toxicology","volume":"13","author":"Bolton","year":"2000","journal-title":"Chem. Res. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1021\/tx700429v","article-title":"Assessment of the Metabolism and Intrinsic Reactivity of a Novel Catechol Metabolite","volume":"21","author":"Hutzler","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4876","DOI":"10.1158\/1078-0432.CCR-10-0748","article-title":"Phase I Safety, Pharmacokinetics, and Inhibition of Src Activity Study of Saracatinib in Patients with Solid Tumors","volume":"16","author":"Baselga","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1007\/s10637-012-9809-7","article-title":"First report of the safety, tolerability, and pharmacokinetics of the Src kinase inhibitor saracatinib (AZD0530) in Japanese patients with advanced solid tumours","volume":"31","author":"Fujisaka","year":"2012","journal-title":"Investig. New Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.molonc.2009.01.002","article-title":"Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530","volume":"3","author":"Green","year":"2009","journal-title":"Mol. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1517\/13543784.2010.499898","article-title":"Novel dual Src\/Abl inhibitors for hematologic and solid malignancies","volume":"19","author":"Schenone","year":"2010","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1038\/bjc.2012.158","article-title":"Phase I study of saracatinib (AZD0530) in combination with paclitaxel and\/or carboplatin in patients with solid tumours","volume":"106","author":"Kaye","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1962","DOI":"10.1007\/s10637-011-9754-x","article-title":"Phase I open-label study of cediranib, an oral inhibitor of VEGF signalling, in combination with the oral Src inhibitor saracatinib in patients with advanced solid tumours","volume":"30","author":"Trarbach","year":"2011","journal-title":"Investig. New Drugs"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7760","DOI":"10.1111\/febs.16197","article-title":"Src family kinases (SFKs): Critical regulators of microglial homeostatic functions and neurodegeneration in Parkinson\u2019s and Alzheimer\u2019s diseases","volume":"289","author":"Portugal","year":"2021","journal-title":"FEBS J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1073\/pnas.77.3.1311","article-title":"Transforming gene product of Rous sarcoma virus phosphorylates tyrosine","volume":"77","author":"Hunter","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/nrc1366","article-title":"A renaissance for SRC","volume":"4","author":"Yeatman","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/35073094","article-title":"The hunting of the Src","volume":"2","author":"Martin","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1016\/S0092-8674(03)00194-6","article-title":"Structural Basis for the Autoinhibition of c-Abl Tyrosine Kinase","volume":"112","author":"Nagar","year":"2003","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6365","DOI":"10.1038\/onc.2008.250","article-title":"Src family kinase oncogenic potential and pathways in prostate cancer as revealed by AZD0530","volume":"27","author":"Chang","year":"2008","journal-title":"Oncogene"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s10549-005-9120-9","article-title":"Elevated Src activity promotes cellular invasion and motility in tamoxifen resistant breast cancer cells","volume":"97","author":"Hiscox","year":"2005","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4165","DOI":"10.1158\/1078-0432.CCR-10-0066","article-title":"Gene Array and Fluorescence In situ Hybridization Biomarkers of Activity of Saracatinib (AZD0530), a Src Inhibitor, in a Preclinical Model of Colorectal Cancer","volume":"16","author":"Arcaroli","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4284","DOI":"10.1158\/1078-0432.CCR-07-5226","article-title":"Combined Inhibition of c-Src and Epidermal Growth Factor Receptor Abrogates Growth and Invasion of Head and Neck Squamous Cell Carcinoma","volume":"14","author":"Koppikar","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1097\/CAD.0b013e3281721ff6","article-title":"Src kinase inhibitors induce apoptosis and mediate cell cycle arrest in lymphoma cells","volume":"18","author":"Nowak","year":"2007","journal-title":"Anti-Cancer Drugs"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1097\/JTO.0b013e31819c78fb","article-title":"The Src Inhibitor AZD0530 Blocks Invasion and May Act as a Radiosensitizer in Lung Cancer Cells","volume":"4","author":"Purnell","year":"2009","journal-title":"J. Thorac. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.bone.2011.12.017","article-title":"Effects of Src kinase inhibition by saracatinib (AZD0530) on bone turnover in advanced malignancy in a Phase I study","volume":"50","author":"Hannon","year":"2012","journal-title":"Bone"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.cllc.2013.08.001","article-title":"A Phase II Trial of Saracatinib, an Inhibitor of src Kinases, in Previously-Treated Advanced Non\u2013Small-Cell Lung Cancer: The Princess Margaret Hospital Phase II Consortium","volume":"15","author":"Laurie","year":"2014","journal-title":"Clin. Lung Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"26090","DOI":"10.18632\/oncotarget.4636","article-title":"Src inhibitors act through different mechanisms in Non-Small Cell Lung Cancer models depending on EGFR and RAS mutational status","volume":"6","author":"Formisano","year":"2015","journal-title":"Oncotarget"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s10549-023-06873-8","article-title":"Aromatase inhibition plus\/minus Src inhibitor saracatinib (AZD0530) in advanced breast cancer therapy (ARISTACAT): A randomised phase II study","volume":"199","author":"Oswald","year":"2023","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e13074","DOI":"10.1200\/jco.2010.28.15_suppl.e13074","article-title":"Phase IB pharmacokinetic (PK) study of Src kinase inhibitor AZD0530 plus anastrozole in postmenopausal hormone receptor positive (HR+) metastatic breast cancer (MBC)","volume":"28","author":"Pegram","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s10549-008-0058-6","article-title":"Dual targeting of Src and ER prevents acquired antihormone resistance in breast cancer cells","volume":"115","author":"Hiscox","year":"2008","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7935475","DOI":"10.1155\/2020\/7935475","article-title":"Results of a Randomized, Double-Blinded, Placebo-Controlled, Phase 2.5 Study of Saracatinib (AZD0530), in Patients with Recurrent Osteosarcoma Localized to the Lung","volume":"2020","author":"Baird","year":"2020","journal-title":"Sarcoma"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s10637-012-9897-4","article-title":"Phase II study of the Src kinase inhibitor saracatinib (AZD0530) in metastatic melanoma","volume":"31","author":"Gangadhar","year":"2012","journal-title":"Investig. New Drugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.clbc.2011.03.021","article-title":"Phase II Trial of Saracatinib (AZD0530), an Oral SRC-inhibitor for the Treatment of Patients with Hormone Receptor-negative Metastatic Breast Cancer","volume":"11","author":"Gucalp","year":"2011","journal-title":"Clin. Breast Cancer"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1007\/s10637-011-9650-4","article-title":"A phase II trial of the Src kinase inhibitor saracatinib (AZD0530) in patients with metastatic or locally advanced gastric or gastro esophageal junction (GEJ) adenocarcinoma: A trial of the PMH phase II consortium","volume":"30","author":"Mackay","year":"2011","journal-title":"Investig. New Drugs"},{"key":"ref_46","first-page":"249","article-title":"Phase II study of saracatinib (AZD0530) for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)","volume":"31","author":"Fury","year":"2011","journal-title":"Anticancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1007\/s10637-010-9611-3","article-title":"A phase I\/II study of the Src inhibitor saracatinib (AZD0530) in combination with gemcitabine in advanced pancreatic cancer","volume":"30","author":"Renouf","year":"2010","journal-title":"Investig. New Drugs"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1007\/s10637-015-0257-z","article-title":"Phase II study of saracatinib (AZD0530) in patients with previously treated metastatic colorectal cancer","volume":"33","author":"Reddy","year":"2015","journal-title":"Investig. New Drugs"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1097\/CAD.0b013e328325a867","article-title":"A phase II trial of the Src-kinase inhibitor AZD0530 in patients with advanced castration-resistant prostate cancer: A California Cancer Consortium study","volume":"20","author":"Lara","year":"2009","journal-title":"Anti-Cancer Drugs"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1093\/annonc\/mdu363","article-title":"A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer","volume":"25","author":"McNeish","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.lungcan.2015.04.008","article-title":"A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies","volume":"89","author":"Gubens","year":"2015","journal-title":"Lung Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1093\/annonc\/mdw014","article-title":"A randomized, double-blind phase II study evaluating cediranib versus cediranib and saracatinib in patients with relapsed metastatic clear-cell renal cancer (COSAK)","volume":"27","author":"Powles","year":"2016","journal-title":"Ann. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.lungcan.2014.03.004","article-title":"A phase II trial of the Src-kinase inhibitor saracatinib after four cycles of chemotherapy for patients with extensive stage small cell lung cancer: NCCTG trial N-0621","volume":"85","author":"Molina","year":"2014","journal-title":"Lung Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4722","DOI":"10.18632\/oncotarget.23524","article-title":"Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer","volume":"9","author":"McGivern","year":"2017","journal-title":"Oncotarget"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.7150\/thno.11543","article-title":"MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer","volume":"5","author":"Bertoli","year":"2015","journal-title":"Theranostics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.abb.2018.03.015","article-title":"miR-19b-3p inhibits breast cancer cell proliferation and reverses saracatinib-resistance by regulating PI3K\/Akt pathway","volume":"645","author":"Jin","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/alzrt238","article-title":"Fyn kinase inhibition as a novel therapy for Alzheimer\u2019s disease","volume":"6","author":"Nygaard","year":"2014","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.biopsych.2017.08.001","article-title":"Modulation of \u03b3- and \u03b2-Secretases as Early Prevention Against Alzheimer\u2019s Disease","volume":"83","author":"Voytyuk","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"112915","DOI":"10.1016\/j.ejmech.2020.112915","article-title":"Small molecule therapeutics for tauopathy in Alzheimer\u2019s disease: Walking on the path of most resistance","volume":"209","author":"Wang","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.biopsych.2017.06.004","article-title":"Targeting Fyn Kinase in Alzheimer\u2019s Disease","volume":"83","author":"Nygaard","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1124\/jpet.114.216044","article-title":"Therapeutic Targeting of Src Kinase in Myofibroblast Differentiation and Pulmonary Fibrosis","volume":"351","author":"Hu","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1021\/cb300655w","article-title":"Development of an ALK2-Biased BMP Type I Receptor Kinase Inhibitor","volume":"8","author":"Mohedas","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1038\/nm.1888","article-title":"BMP type I receptor inhibition reduces heterotopic ossification","volume":"14","author":"Yu","year":"2008","journal-title":"Nat. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"10058","DOI":"10.1523\/JNEUROSCI.0302-15.2015","article-title":"Fyn Kinase Regulates Microglial Neuroinflammatory Responses in Cell Culture and Animal Models of Parkinson\u2019s Disease","volume":"35","author":"Panicker","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Sharma, S., Carlson, S., Gregory-Flores, A., Hinojo-Perez, A., Olson, A., and Thippeswamy, T. (2021). Mechanisms of disease-modifying effect of saracatinib (AZD0530), a Src\/Fyn tyrosine kinase inhibitor, in the rat kainate model of temporal lobe epilepsy. Neurobiol. Dis., 156.","DOI":"10.1016\/j.nbd.2021.105410"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.ajpath.2019.10.012","article-title":"Necroptosis in the Pathophysiology of Disease","volume":"190","author":"Khoury","year":"2019","journal-title":"Am. J. Pathol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41419-024-06514-y","article-title":"Saracatinib inhibits necroptosis and ameliorates psoriatic inflammation by targeting MLKL","volume":"15","author":"Li","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_68","unstructured":"Furumoto, Y., Gomez, G., Gonzalez-Espinosa, C., Kovarova, M., Odom, S., Ryan, J.J., and Rivera, J. (2005). Mast Cells and Basophils: Development, Activation and Roles in Allergic\/Autoimmune Disease: Novartis Foundation Symposium 271, John Wiley & Sons, Ltd.. discussion 47\u201353, 95\u201399."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1038\/nm.1883","article-title":"Treatment of inflammatory and neuropathic pain by uncoupling Src from the NMDA receptor complex","volume":"14","author":"Liu","year":"2008","journal-title":"Nat. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1093\/bib\/bbx017","article-title":"A review of network-based approaches to drug repositioning","volume":"19","author":"Shahreza","year":"2017","journal-title":"Briefings Bioinform."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1164\/rccm.202010-3832OC","article-title":"Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis","volume":"206","author":"Ahangari","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5637","DOI":"10.1038\/s41467-022-33193-0","article-title":"Airway basal cells show a dedifferentiated KRT17highPhenotype and promote fibrosis in idiopathic pulmonary fibrosis","volume":"13","author":"Jaeger","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/s41419-020-2229-2","article-title":"Targeting Src family kinase member Fyn by Saracatinib attenuated liver fibrosis in vitro and in vivo","volume":"11","author":"Du","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Smilde, B.J., Stockklausner, C., Keen, R., Whittaker, A., Bullock, A.N., von Delft, A., van Schoor, N.M., Yu, P.B., and Eekhoff, E.M.W. (2022). Protocol paper: A multi-center, double-blinded, randomized, 6-month, placebo-controlled study followed by 12-month open label extension to evaluate the safety and efficacy of Saracatinib in Fibrodysplasia Ossificans Progressiva (STOPFOP). BMC Musculoskelet. Disord., 23.","DOI":"10.1186\/s12891-022-05471-x"},{"key":"ref_75","first-page":"e95042","article-title":"Saracatinib is an efficacious clinical candidate for fibrodysplasia ossificans progressiva","volume":"6","author":"Williams","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"100261","DOI":"10.1016\/j.jbo.2019.100261","article-title":"An exploratory randomized-controlled trial of the efficacy of the Src-kinase inhibitor saracatinib as a novel analgesic for cancer-induced bone pain","volume":"19","author":"Danson","year":"2019","journal-title":"J. Bone Oncol."},{"key":"ref_77","first-page":"339","article-title":"Anti-allergic effect of the Src family kinase inhibitor saracatinib","volume":"75","author":"Yamaki","year":"2020","journal-title":"Die Pharm.-Int. J. Pharm. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s13045-018-0623-3","article-title":"Combating head and neck cancer metastases by targeting Src using multifunctional nanoparticle-based saracatinib","volume":"11","author":"Lang","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/s13045-019-0827-1","article-title":"Simultaneously inactivating Src and AKT by saracatinib\/capivasertib co-delivery nanoparticles to improve the efficacy of anti-Src therapy in head and neck squamous cell carcinoma","volume":"12","author":"Lang","year":"2019","journal-title":"J. Hematol. Oncol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"30066","DOI":"10.18632\/oncotarget.25700","article-title":"Combined inhibition of PI3K and Src kinases demonstrates synergistic therapeutic efficacy in clear-cell renal carcinoma","volume":"9","author":"Roelants","year":"2018","journal-title":"Oncotarget"},{"key":"ref_81","first-page":"3625","article-title":"Synergistic effect of STAT3-targeted small interfering RNA and AZD0530 against glioblastoma in vitro and in vivo","volume":"20","author":"Liu","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1210487","DOI":"10.3389\/fonc.2023.1210487","article-title":"Saracatinib synergizes with enzalutamide to downregulate AR activity in CRPC","volume":"13","author":"White","year":"2023","journal-title":"Front. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4565\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:32:11Z","timestamp":1760106731000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4565"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,22]]},"references-count":82,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25084565"],"URL":"https:\/\/doi.org\/10.3390\/ijms25084565","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,22]]}}}