Researchers from Oncovalent Therapeutics Inc. recently provided details on the discovery and preclinical evaluation of SB-4826, a first-in-class oral, covalent small-molecule inhibitor of the SUMO activating enzyme (SUMO E1), the initiating enzyme of the sumoylation cascade. Sumoylation is involved in diverse cell processes such as inflammation, DNA damage response, signaling and cell survival/apoptosis, and it has also emerged as a novel target for activating antitumor immunity due to its role in regulating type I interferon (IFN) signaling.