Name: Bosutinib
Synonyms: BOSULIF®, PF-5208763, SKI-606
Chemical Name: 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile
Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease, Dementia with Lewy Bodies
U.S. FDA Status: Alzheimer's Disease (Phase 2), Dementia with Lewy Bodies (Phase 2)
Company: Pfizer
Approved for: Chronic myeloid leukemia


Bosutinib is an oral inhibitor of Abl and Src tyrosine kinases that has been approved since 2012 for the treatment of chronic myeloid leukemia. Its common side effects are diarrhea, nausea, and vomiting. The drug can also cause myelosuppression.

Bosutinib and another Abl inhibitor, nilotinib, are candidates for repurposing to treat the α-synucleinopathies Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), and other neurodegenerative conditions. The inhibitors promote autophagy, which facilitates clearance of neurotoxic protein aggregates in neurons.

In preclinical work, bosutinib reduced levels of α-synuclein in mice expressing the human A53T α-synuclein pathogenic mutation. Bosutinib was reported to enhance dopaminergic neuron survival, and modulated the immune response to α-synuclein (Lonskaya et al., 2013; Hebron et al., 2014).

In other mouse models, bosutinib treatment facilitated α-amyloid and tau clearance, changes in immune markers, and cognitive improvement (Lonskaya et al., 2013; Lonskaya et al., 2015Hebron et al., 2018). The drug also protected against TDP-43 toxicity in mice (Heyburn et al., 2016; Wenqiang et al., 2014). 

In cell and animal models of amyotrophic lateral sclerosis, bosutinib enhanced survival and function of motor neurons (Imamura et al., 2017; Osaki et al., 2018).


In September 2016, a Phase 1, open-label study began to evaluate bosutinib’s tolerability in people with mild cognitive impairment or dementia. The single-center study at a private neurological practice in Santa Monica, California, has enrolled 71 volunteers between age 45 and 89 with a Clinical Dementia Rating from 0.5 to 2. Participants start out on 100 mg bosutinib daily, with the dose increasing monthly to a top dose of 300 mg as tolerated. Total treatment time is one year, and the primary outcome is the number of patients who discontinue treatment due to side effects. A publication describes results of dementia evaluation on 31 participants who completed one year of treatment and one year of follow-up (Mahdavi et al., 2021). The patients had probable AD dementia or Parkinson's dementia. During the year of treatment, participants declined less according to the Quick Dementia Rating System and the Repeatable Battery Assessment of Neuropsychological Status, than expected from population estimates. No difference was found on the MoCA. Sixteen patients reached one year of follow-up; as a group, their worsening was no different than the population-based estimate. The trial will run through December 2023.

In April 2019, a Phase 2 trial began testing bosutinib in people with DLB. The single-center study at Georgetown University, Washington, D.C., will enroll 30 patients for a 12-week regimen of 100 mg drug or placebo per day, followed by a four-week follow-up. The primary outcome is safety and tolerability. Secondary measures include plasma and CSF bosutinib levels and changes in a panel of plasma and CSF biomarkers including dopamine metabolites, Aβ, total and phosphorylated tau, oligomeric α-synuclein, as well as additional markers of cell death and inflammation. The trial was expected to finish in August 2021.

An open-label Phase 1 study in ALS patients is underway in Japan. In March 2019, Kyoto University investigators began recruiting 24 patients to compare treatment with 100, 200, 300, or 400 mg/day bosutinib for 12 weeks, with a four-week follow-up (Imamura et al., 2019). The primary outcome is the occurrence of dose-limiting toxicity during treatment or follow-up. The trial will also measure change from baseline in lung function and grip strength, and blood levels of neurofilament proteins. The study will finish in 2022. 

Bosutinib is also being evaluated in other types of cancer. For details on bosutinib trials, see

Last Updated: 24 Jan 2022


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Therapeutics Citations

  1. Nilotinib

Research Models Citations

  1. α-synuclein A53T Mouse (Tg)

Paper Citations

  1. . Treatment of Dementia With Bosutinib: An Open-Label Study of a Tyrosine Kinase Inhibitor. Neurol Clin Pract. 2021 Jun;11(3):e294-e302. PubMed.
  2. . Induced pluripotent stem cell-based Drug Repurposing for Amyotrophic lateral sclerosis Medicine (iDReAM) study: protocol for a phase I dose escalation study of bosutinib for amyotrophic lateral sclerosis patients. BMJ Open. 2019 Dec 2;9(12):e033131. PubMed.
  3. . Ubiquitination increases parkin activity to promote autophagic α-synuclein clearance. PLoS One. 2013;8(12):e83914. Epub 2013 Dec 26 PubMed.
  4. . Tyrosine Kinase Inhibition Regulates Early Systemic Immune Changes and Modulates the Neuroimmune Response in α-Synucleinopathy. J Clin Cell Immunol. 2014 Sep 30;5:259. PubMed.
  5. . Tyrosine kinase inhibition increases functional parkin-Beclin-1 interaction and enhances amyloid clearance and cognitive performance. EMBO Mol Med. 2013 Aug;5(8):1247-62. PubMed.
  6. . Nilotinib and bosutinib modulate pre-plaque alterations of blood immune markers and neuro-inflammation in Alzheimer's disease models. Neuroscience. 2015 Sep 24;304:316-27. Epub 2015 Jul 30 PubMed.
  7. . Tau clearance improves astrocytic function and brain glutamate-glutamine cycle. J Neurol Sci. 2018 Aug 15;391:90-99. Epub 2018 Jun 12 PubMed.
  8. . Tyrosine kinase inhibition reverses TDP-43 effects on synaptic protein expression, astrocytic function and amino acid dis-homeostasis. J Neurochem. 2016 Nov;139(4):610-623. Epub 2016 Sep 27 PubMed.
  9. . Parkin-mediated reduction of nuclear and soluble TDP-43 reverses behavioral decline in symptomatic mice. Hum Mol Genet. 2014 Sep 15;23(18):4960-9. Epub 2014 May 8 PubMed.
  10. . The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis. Sci Transl Med. 2017 May 24;9(391) PubMed.
  11. . Microphysiological 3D model of amyotrophic lateral sclerosis (ALS) from human iPS-derived muscle cells and optogenetic motor neurons. Sci Adv. 2018 Oct;4(10):eaat5847. Epub 2018 Oct 10 PubMed.

External Citations

  1. Phase 1 study

Further Reading


  1. . Nilotinib - Differentiating the Hope from the Hype. J Parkinsons Dis. 2016 Jul 12;6(3):519-22. PubMed.
  2. . Pharmacokinetics and pharmacodynamics of a single dose Nilotinib in individuals with Parkinson's disease. Pharmacol Res Perspect. 2019 Apr;7(2):e00470. Epub 2019 Mar 12 PubMed.
  3. . Multikinase Abl/DDR/Src Inhibition Produces Optimal Effects for Tyrosine Kinase Inhibition in Neurodegeneration. Drugs R D. 2019 Jun;19(2):149-166. PubMed.
  4. . Cell models of lipid-rich α-synuclein aggregation validate known modifiers of α-synuclein biology and identify stearoyl-CoA desaturase. Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20760-20769. Epub 2019 Sep 23 PubMed.
  5. . Targeting kinases in Parkinson's disease: A mechanism shared by LRRK2, neurotrophins, exenatide, urate, nilotinib and lithium. J Neurol Sci. 2019 Jul 15;402:121-130. Epub 2019 May 15 PubMed.
  6. . BMS-708163 and Nilotinib restore synaptic dysfunction in human embryonic stem cell-derived Alzheimer's disease models. Sci Rep. 2016 Sep 19;6:33427. PubMed.
  7. . Nilotinib and bosutinib modulate pre-plaque alterations of blood immune markers and neuro-inflammation in Alzheimer's disease models. Neuroscience. 2015 Sep 24;304:316-27. Epub 2015 Jul 30 PubMed.