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Name: Saracatinib
Synonyms: AZD0530
Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease, Parkinson's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued), Parkinson's Disease (Phase 1)
Company: AstraZeneca


Saracatinib is an inhibitor of the Src/abl family of kinases. It was originally developed by AstraZeneca for various types of cancer, but discontinued in Phase 2 for lack of efficacy. The Discovering New Therapeutic Uses program at the National Center for Advancing Translational Sciences (NCATS) funded a grant to Stephen Strittmatter and colleagues at Yale University to explore the clinical use of saracatinib for Alzheimer's through Phase 2a. Through its Open Innovation Initiative, AstraZeneca agreed to supply the drug and matching placebo for clinical trials in Alzheimer's disease (see NIH Director's blog).

The rationale for this repurposing grew out of work on the tyrosine kinase Fyn. This member of the src kinase family is expressed in the brain and involved in signal transduction pathways underpinning synaptic plasticity. Fyn is believed to mediate Aβ toxicity. For example, it has been reported to become activated in the postsynapse in response to interactions at the postsynaptic plasma membrane between oligomeric Aβ, the prion protein, and the metabotropic glutamate receptor mGluR5. A separate line of evidence has linked Fyn to tau; reporting, for example, that Fyn phosphorylates dendritic tau, which then localizes Fyn to the postsynaptic density (Um, et al. 2012Ittner et al., 2010; for review see Nygaard et al., 2014). Fyn has also been implicated in aspects of Parkinson’s disease pathogenesis and levodopa-induced dyskinesia (reviewed in Angelopoulou et al., 2022).

Preclinical treatment studies reported that AZD0530 blocked Fyn in brain slices, rescued synaptic depletion and spatial memory deficits in APP/PS1 mice, and that the treatment effect persisted after drug washout (Kaufman et al., 2015, Smith et al., 2018). In the same mouse line, AZD0530 was reported to boost hippocampal synaptic density, as measured with a PET ligand that binds synaptic vesicle glycoprotein 2A (Toyonaga et al., 2019). AZD0530 inhibited tau hyperphosphorylation and oligomerization in cell-based assays (Yadikar et al., 2020). In animal models of tauopathy, it reduced accumulation of hippocampal p-tau and glial activation, promoted recovery of synaptic markers, and prevented memory and learning deficits (Tang et al., 2020).


In July 2013, a Phase 1b multiple-ascending-dose study at Yale began evaluating a one-month course of 50 to 125 mg AZD0530 taken once daily by 24 people with mild to moderate Alzheimer's disease. One primary goal was to confirm the safety of a one-month course of saracatinib, as previously found in oncology trials; the other was to quantify how well the drug penetrated the blood-brain barrier. In April 2015, the drug was reported to have been "reasonably safe and well-tolerated" in this study, although one case of congestive heart failure and pneumonia on the highest dose was considered possibly related to saracatinib. The ratio of plasma to CSF drug levels was reported to be 0.4 and dose-dependent, indicating brain penetration. The 100mg and 125mg doses achieved CSF levels corresponding to brain levels that rescued memory deficits in transgenic AD mouse models (Kaufman et al., 2015). This four-week treatment regimen did not affect secondary outcome measures of cognition or behavioral function, activities of daily living, or brain activity as measured by FDG-PET (Nygaard et al., 2015).

In December 2014, a 159-patient Phase 2a study began. Called Connect, this 22-center study uses the Alzheimer's Disease Cooperative Study infrastructure to compare a 12-month course of 100 and 125 mg AZD0530 to placebo. A two-week plasma level is used to adjust dose. This trial ascertains the clinical AD diagnosis by way of amyloid imaging. Its twin primary outcome measures are cerebral glucose metabolism and safety; secondary measures include cognitive and behavioral measures, as well as imaging and fluid biomarker measures and influence of ApoE genotype on the treatment effects.

The trial ended in March 2018, and at CTAD2018, the investigators reported the drug did not slow the decline in cerebral glucose metabolism compared to placebo, or change any other outcomes (Nov 2018 news). There was a trend towards less shrinkage of the hippocampus and entorhinal cortex in the treated group. Saracatinib caused diarrhea and other gastrointestinal side effects, and one quarter of treated participants dropped out before the end of the trial. Results were published in a peer reviewed journal (Van Dyck et al., 2019).

In April 2019, a phase crossover 1 study began enrolling 30 people with Parkinson's disease accompanied by delusions or hallucinations to compare a 14 day course of 100 mg saracatinib to placebo. Outcomes include fMRI and other brain imaging and EEG measures of visual processing, as well as change on functional scales measuring non-motor and psychiatric symptoms of PD. This trial was to run at King's College London, until September 2021.

Outside of various types of cancer, saracatinib was also trialed in alcoholism, and currently is in testing for pulmonary fibrosis. For all trials on this compound, see

Clinical Trial Timeline

  • Phase 2
  • Study completed / Planned end date
  • Planned end date unavailable
  • Study aborted
Sponsor Clinical Trial 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 2025 2026 2027 2028 2029 2030 2031 2032 2033 2034
Yale University NCT02167256

Last Updated: 24 Jul 2023


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News Citations

  1. Fits and Starts: Trial Results from the CTAD Conference

Paper Citations

  1. . Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Ann Neurol. 2015 Jun;77(6):953-71. Epub 2015 Mar 21 PubMed.
  2. . A phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer's disease. Alzheimers Res Ther. 2015;7(1):35. Epub 2015 Apr 14 PubMed.
  3. . Effect of AZD0530 on Cerebral Metabolic Decline in Alzheimer Disease: A Randomized Clinical Trial. JAMA Neurol. 2019 Jul 22; PubMed.
  4. . Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nat Neurosci. 2012 Sep;15(9):1227-35. Epub 2012 Jul 22 PubMed.
  5. . Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell. 2010 Aug 6;142(3):387-97. Epub 2010 Jul 22 PubMed.
  6. . Fyn kinase inhibition as a novel therapy for Alzheimer's disease. Alzheimers Res Ther. 2014;6(1):8. Epub 2014 Feb 5 PubMed.
  7. . Pivotal Role of Fyn Kinase in Parkinson's Disease and Levodopa-Induced Dyskinesia: a Novel Therapeutic Target?. Mol Neurobiol. 2021 Apr;58(4):1372-1391. Epub 2020 Nov 11 PubMed.
  8. . Disease-modifying benefit of Fyn blockade persists after washout in mouse Alzheimer's model. Neuropharmacology. 2018 Mar 1;130:54-61. Epub 2017 Nov 27 PubMed.
  9. . In vivo synaptic density imaging with 11C-UCB-J detects treatment effects of saracatinib (AZD0530) in a mouse model of Alzheimer's disease. J Nucl Med. 2019 May 17; PubMed.
  10. . Screening of tau protein kinase inhibitors in a tauopathy-relevant cell-based model of tau hyperphosphorylation and oligomerization. PLoS One. 2020;15(7):e0224952. Epub 2020 Jul 21 PubMed.
  11. . Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy. Acta Neuropathol Commun. 2020 Jul 1;8(1):96. PubMed.

External Citations

  2. Open Innovation Initiative
  3. NIH Director's blog

Further Reading


  1. . An update on dual Src/Abl inhibitors. Future Med Chem. 2012 Apr;4(6):799-822. PubMed.