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Notably, Trp-catabolism is well recognized to be linked to inflammation, immune response and inflammatory diseases 44,45,46

BEACON CRC (binimetinib [BINI], encorafenib [ENCO], and cetuximab [CTX] combined to treat BRAF-mutant metastatic colorectal cancer [mCRC]): A multicenter, randomized, open-label, three-arm phase III study of ENCO plus CTX plus or minus BINI vs irinotecan (IRI)/CTX or infusional 5-fluorouracil/folinic acid/IRI (FOLFIRI)/CTX with a safety lead-in of ENCO + BINI + CTX in patients (Pts) with BRAFV600E mCRC

J Biol Chem 277:4235842365

This kind of compounds shows a high specificity for IRAP against APN (Compound 8 IC 50 = 5.8 M) and according to docking studies, the inhibitor acts in a binding pocket close to the GAMEN loop without interacting with the zing atom, leading to uncompetitive inhibition, confirmed later on by kinetic studies

Snyder RJ, Cardinal M, Dauphinee D, Stavosky J