G721-0377 is a next-generation small molecule inhibitor of chitinase-3 like-protein-1 (CHI3L1, YKL-40) with binding Kd of 45 uM.
G721-0377 exhibited favorable pharmacokinetic properties, including improved solubility, balanced permeability, reduced microsomal clearance, and an enhanced cardiac safety margin.
G721-0377 reversed CHI3L1-induced astrocytic dysfunction, restoring amyloid uptake, lysosomal proteolysis and acidification, suppressing CHI3L1 and IL-6 secretion, and inhibiting NF-κB activation to levels comparable to a neutralizing anti-CHI3L1 antibody.
