IDO-PROTAC

IDO-PROTAC is a proteolysis-targeting chimera (PROTAC) designed to induce the degradation of Indoleamine 2,3-dioxygenase 1 (IDO1). Developed by researchers at Northwestern University, the molecule utilizes a binder derived from the IDO1 inhibitor BMS-986205 (linrodostat) coupled via a linker to an E3 ubiquitin ligase ligand, specifically targeting cereblon (CRBN). Unlike traditional IDO inhibitors that only block the enzyme's catalytic conversion of tryptophan to kynurenine, IDO-PROTAC facilitates the ubiquitination and proteasomal degradation of the entire IDO1 protein. This approach aims to neutralize both the metabolic and non-enzymatic immunosuppressive functions of IDO1, which are implicated in tumor immune evasion. Preclinical studies in glioblastoma models have demonstrated that the compound can penetrate the blood-brain barrier and degrade IDO1 in both tumor and non-tumor cells, potentially enhancing the efficacy of other immunotherapies.

Other names

IDO-proteolysis targeting chimeraIDO-protein degrader