GSK583

GSK583 (CAS No.: 1346547-00-9) is a highly potent, selective, and orally active small-molecule inhibitor of receptor-interacting protein kinase 2 (RIP2, also known as RICK), a key mediator of innate immune signaling downstream of the pattern recognition receptors NOD1 and NOD2. By competitively inhibiting RIP2 kinase activity, GSK583 disrupts signaling cascades that regulate pro-inflammatory cytokine production, thereby attenuating downstream transcriptional responses. It exhibits strong biochemical potency with inhibitory activity in the low nanomolar range and effectively suppresses the production of inflammatory cytokines such as TNF-α and IL-6 in cellular and ex vivo systems at submicromolar concentrations. Given the central role of RIP2 in immune cell activation and inflammatory signaling pathways, GSK583 is widely used as a pharmacological tool for investigating mechanisms of innate immunity, cytokine regulation, and host–pathogen interactions, as well as for validating therapeutic targets in inflammatory and immune-mediated disease models. Experimental concentrations and dosing regimens vary depending on the specific cellular context, tissue model, or in vivo study design.