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SRI-42127 is a HuR translocation inhibitor. HuR is an RNA regulator that binds to AREs, and HuR translocations promote the production of inflammatory cytokines in glial cells. However, SRI-42127 can destroy mRNA stability and inhibit gene promoter activation. SRI-42127 also inhibits microglial cell activation and attenuates recruitment/chemotaxis of neutrophils and monocytes[1].

SRI-42127 is a blood-brain barrier permeable imidazopyridazinamine analog th at potently and reversibly inhibits the RNA-binding protein HuR multimerization and blocks HuR nucleocytoplasmic shuttling. SRI-42127 suppresses the expression and release of several pro-inflammatory mediators with minimal effect on anti-inflammatory cytokines. SRI 42127 weakens HuR interaction with Bcl-2 and Mcl-1 leading to induction of apoptosis and decreased tumor growth. SRI42127 subdues microglial activation in vivo and attenuates the recruitment/chemotaxis of neutrophils and monocytes.

[1] Chellappan R, et al. SRI-42127, a novel small molecule inhibitor of the RNA regulator HuR, potently attenuates glial activation in a model of lipopolysaccharide-induced neuroinflammation. Glia. 2022 Jan;70(1):155-172. DOI:10.1002/glia.24094