Description
Saracatinib is a dual inhibitor of the tyrosine kinases c-
Src and Abl (IC
50 = 2.7 and 30 nM, respectively). It less effectively inhibits other receptor and non-
receptor tyrosine kinases as well as assorted serine/threonine kinases. Saracatinib is orally available and blocks cell motility, migration, adhesion, invasion, proliferation, differentiation, and survival. Through its effects on c-
Src, it reduces osteoclast bone resorption. Saracatinib also blocks denque virus RNA replication through its effect on Fyn kinase.
Chemical Properties
White Solid
Uses
An oral, selective dual inhibitor of Src and ABL kinase. It is a COVID19-related research product.
Definition
ChEBI: Saracatinib is a member of the class of quinazolines that is quinazoline substituted by (5-chloro-2H-1,3-benzodioxol-4-yl)amino, (oxan-4-yl)oxy and 2-(4-methylpiperazin-1-yl)ethoxy groups at positions 4, 5 and 7, respectively. It is a dual inhibitor of the tyrosine kinases c-Src and Abl (IC50 = 2.7 and 30 nM, respectively). Saracatinib was originally developed by AstraZeneca for the treatment of cancer but in 2019 it was granted orphan drug designation by the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis (IPF), a type of lung disease that results in scarring (fibrosis) of the lungs. It has a role as an antineoplastic agent, an EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor, a radiosensitizing agent, an autophagy inducer, an apoptosis inducer and an anticoronaviral agent. It is a member of quinazolines, a secondary amino compound, a N-methylpiperazine, an aromatic ether, a member of oxanes, a member of benzodioxoles, an organochlorine compound and a diether.
References
Hennequin et al. (2006), 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; J. Med. Chem., 49 6465
Green et al. (2009), Preclinical anticancer activity of the potent, oral Src inhibitor AZD0530; Oncol., 3 248
de Wispelaere et al. (2013), The small molecules AZD0530 and Dasatinib inhibit dengue virus RNA replication via Fyn kinase; Virol., 87 7367
Shin et al. (2018), Saracatinib Inhibits Middle East Respiratory Syndrome-Coronavirus Replication In Vitro; Viruses, 10 283
Tang et al. (2020), Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic mice and traumatic Tauopathy; Acta Neuropathol. Commun., 8 96
Kaufman et al. (2015), Fyn inhibition rescues established memory and synapse loss in Alzheimer mice; Neurol., 77 953
