Laquinimod

Laquinimod (ABR-215062), an orally available carboxamide derivative, is a potent immunomodulator which prevents neurodegeneration and inflammation in the central nervous system. Laquinimod reduces astrocytic NF-κB activation to protect from Cuprizone-induced demyelination. Laquinimod has?the?potential?for relapsing remitting (RR) and chronic progressive (CP) forms of multiple sclerosis (MS; RRMS or CPMS) as well as neurodegenerative diseases?research^[1][2][3][4]. IC50 & Target: NF-κB^[3] In Vitro: Laquinimod reverses EAE and inhibits pathogenic T cell immune responses. Laquinimod reverses RR-EAE and inhibits inflammatory T cell responses via a direct effect on myeloid APC. Laquinimod alters myeloid APC subsets and inhibits Th1 and Th17 polarization of myelin-specific T cells. Laquinimod-induced type II (M2) monocytes reverse established EAE^[1]. Laquinimod modulates the phenotype of B cells of healthy donors. Laquinimod modulates expression of markers related to regulatory capacity in B cells of RRMS patients. Laquinimod reduces IFNγ cytokine expression in CD4⁺ T cells^[2]. In Vivo: Laquinimod treatment inhibits donor myelin-specific T cells from transferring EAE to naive recipient mice. In vivo laquinimod treatment alters subpopulations of myeloid antigen presenting cells (APC) that include a decrease in CD11c⁺CD11b⁺CD4⁺?dendritic cells (DC) and an elevation of CD11b^hiGr1^hi monocytes^[1].