RGNCY-0045 (LDDN-0003499 Src inhibitor)

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LDDN-0003499 is a novel small molecule Src family tyrosine kinase inhibitor with anti-inflammatory effects in response to Aβ stimulation of microglia. It produced a dose dependent decrease in basal levels of active, phosphorylated Src and Lyn in BV2 cells (microglial cell line). LDDN-0003499 treatment also attenuated the Aβ-stimulated increase in active, phosphorylated levels of Lyn/Src and TNFα and IL-6 secretion.  This compound also has properties that suggest oral availability and blood brain barrier penetration.  Furthermore, in vitro/in vivo characterization of LDDN-0003499 as well as structural modification may provide a new tool for attenuating microglial-mediated brain inflammatory conditions such as that occurring in AD.


Systematic Name: N-(2,4-dichlorophenyl)-6,7-dimethoxyquinazolin-4-amine

Formula: C16H13Cl2N3O2

PMID: 26161952

MWT: 350.2

Reference: Gunjan D Manocha, Kendra L Puig et al.  Characterization of novel Src family kinase inhibitors to attenuate microgliosis.  PLOS ONE (2015). 10:10(7):e0132604.

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Tags: Kinase, Alzheimer’s, Alzheimers, Src, Lyn, inflammation, brain, Alzheimer, RGNCY-0045, LDDN, LDDN-0003499, Microglia, TNF, IL-6, BBB