ARI-4175

ARI-4175 is an orally bioavailable small‑molecule pan‑inhibitor of the DASH (dipeptidyl peptidase IV activity and/or structural homologues) family of enzymes, including several prolyl peptidases, being developed as an immunomodulatory anticancer agent.[1][4][6] In multiple murine solid tumor models, ARI-4175 induces immune‑mediated tumor regression and, in some settings, complete eradication with development of immunologic memory, while having little direct cytotoxicity on tumor cells in vitro.[1][4][8] The compound modulates the tumor and immune microenvironment by increasing dendritic cells, natural killer cells, and certain myeloid populations, altering tumor-cell surface phenotype to enhance antigen-specific cytotoxic T‑lymphocyte killing, and shifting myeloid-derived suppressor cell subsets.[1][4] ARI-4175 has shown potent antitumor activity as monotherapy and enhanced efficacy when combined with tumor vaccines, adoptive T‑cell therapy, or cetuximab in KRAS‑mutant colorectal cancer xenografts, supporting its positioning as an immunotherapy-adjuvant DASH/prolyl peptidase inhibitor for solid tumors, including colorectal cancer and sarcomas.[1][2][4][5][6]