LK01003

LK01003 provides a novel tool to study RIPK3 biology. LK01003 is potent in biochemical settings and X-ray crystallographic studies corroborate its mechanism of binding and action. As a key feature, LK01003 does not trigger on-target apoptosis, yet has low single-digit micromolar potency in necroptosis assays; further, LK01003 modulates the levels of phosphorylated RIPK3 in the cell. Although LK01003 presents a very good kinase selectivity profile, caution should be exercised when interpreting results from studies where RIPK2 and/or BRK biology may also be implicated, especially if LK01003 is used at the higher concentration of 10 microM (as those kinases will be inhibited by LK01003 at those levels). Despite LK01003 delivering good activity in cellular context, in the primary reference for LK01003 (doi.org/10.1038/s41467-025-59432-8) there is a mention of an analogue, LK01045, that shows superior potency in cell assays, presumably due to improved physicochemical properties. However, LK01045 is not characterized to the same extent as LK01003.