Dual Drug Repurposing: The Example of Saracatinib

Int J Mol Sci. 2024 Apr 22;25(8):4565. doi: 10.3390/ijms25084565.

Abstract

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's 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's 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.

Keywords: Alzheimer’s disease; cancer; clinical trials; drug repurposing; pre-clinical trials; saracatinib.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Benzodioxoles* / chemistry
  • Benzodioxoles* / pharmacology
  • Benzodioxoles* / therapeutic use
  • Drug Repositioning* / methods
  • Humans
  • Neoplasms / drug therapy
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines* / chemistry
  • Quinazolines* / pharmacology
  • Quinazolines* / therapeutic use
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / metabolism

Substances

  • saracatinib
  • Quinazolines
  • Benzodioxoles
  • Protein Kinase Inhibitors
  • src-Family Kinases
  • Antineoplastic Agents

Grants and funding

This research was financed by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020 Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through Fundação para a Ciência e a Tecnologia (FCT) in the framework of projects IF/00092/2014/CP1255/CT0004 and CHAIR in Onco-Innovation from Faculty of Medicine, University of Porto (FMUP).