DELC2 is a brain-penetrant Chitinase-3-like protein 1 (CHI3L1) inhibitor with MST KD of 10.31 uM, SPR KD of 8.7 uM, inhibits CHI3L1-RAGE association with IC50 of 2.25 uM in ELISA assays, suppresses RAGE-linked inflammatory signaling.
DELC2 reduces CHI3L1-RAGE engagement with IC50 of 2.12 uM in biolayer interferometry (BLI) using a RAGE-Fc biosensor.
DELC2 also engages recombinant murine Chi3l1 using MST.
DELC2 disrupts the CHI3L1-driven astrocyte-microglia inflammatory relay and restores Aβ handling in astrocyte-microglia co-culture system.
DELC2 suppresses CHI3L1-associated inflammatory activity in sourced cerebrospinal fluid (CSF) samples from donors with AD, attenuates the activity of AD CSF in glial cultures, reduces astrocytic Aβ uptake, and increases microglial IL-1β secretion.
DELC2 improves cognitive and amyloid-associated outcomes while suppressing glial inflammatory programs in 5xFAD mice.
DELC2 normalizes cell-resolved astrocyte and microglial inflammatory signaling states in 5xFAD brain.
DELC2 normalizes inflammatory gene-expression programs in FACS-purified astrocytes and microglia from 5xFAD brain.