RGNCY-0063 (SNU-BP PPAR-γ agonist)

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SNU-BP is a novel small molecule that inhibits lipopolysaccharide (LPS)-induced nitric oxide production in microglia.  SNU-BP inhibits pro-inflammatory cytokines and inducible nitric oxide synthase in LPS-stimulated microglia and potentiated interleukin-4 induced arginase-1 expression. SNU-BP specifically activates PPAR-γ and not PPARδ- nor PPAR-α, confirming that PPAR-γ  is the specific target protein for SNU-BP.  The anti-inflammatory effect of SNU-BP is attenuated by pharmacological and genetic inhibition of PPAR-γ .  SNU-BP also induced an anti-inflammatory phenotype in astrocytes by inhibiting pro-inflammatory nitric oxide and TNF-α while increasing anti-inflammatory genes such as arginase-1 and Ym-1. SNU-BP increases the M2-like phenotype of neuroglia. Importantly, SNU-BP produced an anti-inflammatory response in the LPS-injected mouse brain demonstrating a protective potential for neuroinflammatory diseases.

Systematic Name:  2-(4-(5-(1-((benzyl(phenylcarbamoyl)carbamoyl)oxy)propyl)isoxazol-3-yl)phenoxy)-2-methylpropanoic acid 

SMILES: OC(C(C(C)OC1=CC=C(C2=NOC(C(OC(N(C(NC3=CC=CC=C3)=O)

CC4=CC=CC=C4)=O)CC)=C2)C=C1)=O   

Formula:  C31H31N3O7

Mol Wt:  557.60

PMID:  27288982