UNC9995

UNC9995 is a β-arrestin2-biased agonist of dopamine receptor Drd2. UNC9995 inhibits NLRP3 inflammasome activation by enhancing β-arrestin2-NLRP3 interaction, thus prevents neuronal degeneration. Futhermore, UNC9995 activates the Drd2/β-arrestin2 signaling to prevent inflammation-related genes transcription-induced by JAK/STAT3. UNC9995 improves depressive behavior in mouse model, and improves astrocytes dysfunctions^[1]. In Vitro:UNC9995 (10 μM; 1 h) promotes the combination of STAT3 and β-arrestin2, induced by IL-6 (300 ng/mL; 24 h) in primary astrocytes. And it also inhibits activation of STING, TBK1, JAK^[1].
UNC9995 (1, 5, 10, and 20 μM; 1 h) abolishes the apoptosis and inflammation of both WT and Arrb2^−/− astrocytes stimulated with IL-6 (300 ng/mL) for 24 h^[1].
In Vivo:UNC9995 (2 mg/kg/day, i.p, 2 weeks) ameliorates depressive-like behavioral phenotype and improves the loss of astrocytes in the hippocampus in both Chronic social defeated stress (CSDS) model and Chronic unpredictable mild stress (CUMS) model in mouse^[1].