Researchers at iMed Luís Carvalho and Rui Moreira have recently reported the discovery of novel potent and selective inhibitors of the cancer-associated enzyme dipeptidyl peptidase 8 (DPP8), article published in Angewandte Chemie International Edition (IF 2021 = 16,8). This enzyme, together with its analogue DPP9, is particularly known for its key roles in the immune response, cell cycle regulation and chemosensitisation of Leukemia cells to cytotoxic agents.  Luís Carvalho and Rui Moreira, using a multidisciplinary chemical biology approach and in collaboration with an international team, employed a proteomics platform to enable the identification of an unprecedented class of DPP8 inhibitors, unveiling their mechanism of action.

This discovery sets the stage to chemically modulate the immune system to t potentiate antitumor immunity. The search for DPP8 and DPP9 selectivity is a hot topic in chemical biology, and the work reported by the iMed scientists article was highlighted as a hot paper and with a main cover feature in the current issue of Angewandte Chemie