Crisdesalazine

Crisdesalazine (AAD-2004) is a microsomal prostaglandin E₂ synthase-1 (mPGES-1) inhibitor. Crisdesalazine acts as a potent free radical scavenger that directly neutralizes reactive oxygen species (ROS) including hydrogen peroxide, exerting neuroprotective effects against apoptosis and axonal damage. Crisdesalazine inhibits PGE₂ production, mediates inflammatory responses, and promotes the conversion of macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Crisdesalazine is applicable to neuroprotection research in multiple sclerosis and spinal cord injury^[1][2]. In Vitro:Crisdesalazine (0.2-50 μM; 24 h) is non-cytotoxic to murine RAW 264.7 macrophages at concentrations up to 50 μM and to human SH-SY5Y neuroblastoma cells at concentrations up to 10 μM, with reduced viability only at 50 μM in SH-SY5Y cells^[1].
Crisdesalazine (0.2-5 μM; 24 h post-LPS stimulation) promotes the transition of LPS-stimulated murine RAW 264.7 macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype by reducing pro-inflammatory marker and cytokine expression and increasing anti-inflammatory marker expression^[1].
Crisdesalazine (0.2-5 μM; 24 h during co-culture) reduces neuroinflammation and neuronal necrosis in human SH-SY5Y cells co-cultured with LPS-stimulated murine RAW 264.7 macrophages by suppressing pro-inflammatory cytokine expression and decreasing necrotic cell populations^[1].
Crisdesalazine (1 mM) reduces H₂O₂ levels in primary mouse spinal cord astrocytes, attenuates astrocytic reactivity, and exerts neuroprotective effects against apoptosis and axonal injury in primary mouse cortical neurons co-cultured with OGD/R-challenged astrocytes^[2]. In Vivo:Crisdesalazine (3.3 mg/kg; i.p.; daily; 7 days) significantly alleviates clinical symptoms, reduces inflammatory cell infiltration and demyelination, shifts microglia/macrophage polarization toward an anti-inflammatory M2 phenotype, and expands Treg populations in a mouse EAE model of multiple sclerosis^[1].
Crisdesalazine (3.3 mg/kg; i.p.; daily; 14 days) reduces spinal cord H₂O₂ levels, inhibits glial scar formation and astrocyte proliferation, promotes neuronal and axonal regeneration, and improves motor function in a mouse model of spinal cord injury^[2].