TTP488 is an orally bioavailable small molecule that inhibits the receptor for advanced glycation endproducts (RAGE). The compound is being developed for the treatment of Alzheimer’s disease.
The compound blocks endogenous ligands from binding to the receptor.
TTP488 inhibits ligand-mediated effects in a cell-based assay, has a 10:1 brain to plasma ratio in pharmacology models, demonstrates efficacy in an SAA model of amyloidosis, alters plaque burden, learning behavior, and cytokines in a prophylactic mouse model and alters plaque burden, learning behavior, and A-β levels in a therapeutic mouse model.
These data taken together suggest that inhibition of RAGE with an orally available small molecule inhibitor presents an attractive therapeutic rationale for the treatment of Alzheimer’s disease. TTP488 is currently being evaluated in the clinic.