RIPK2 Inhibitor 1

RIPK2 inhibitor 1 is an inhibitor of receptor-interacting serine/threonine kinase 2 (RIPK2; IC₅₀ = 5 nM for the human enzyme) and an active metabolite of the prodrug GSK2983559 (Item No. 31458).¹ It is selective for RIPK2 over a panel of 295 kinases at 1 µM but does inhibit VEGFR3, VEGFR2, ephrin type-A receptor 6 (EphA6), Abl2, and serine/threonine-protein kinase 10 (STK10) by ≥70% at 1 µM. RIPK2 inhibitor 1 is also selective for RIPK2 over a panel of 138 receptors, ion channels, and enzymes but does bind to melatonin receptor 3 (MT₃) at 10 µM. It inhibits TNF-α production induced by the nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist muramyl dipeptide (Item No. 30866) in isolated human whole blood (IC₅₀ = 26 nM). RIPK2 inhibitor 1 reduces IL-1β release in intestinal mucosa explants from patients with Crohn’s disease or ulcerative colitis (IC₅₀ = ^~10 nM for both).

WARNING This product is not for human or veterinary use.

1. Haile, P.A., Casillas, L.N., Votta, B.J., et al. Discovery of a first-in-class receptor interacting protein 2 (RIP2) kinase specific clinical candidate, 2-((4-(benzo[d]thiazol-5-ylamino)-6-(tert-butylsulfonyl)quinazolin-7-yl)oxy)ethyl dihydrogen phosphate, for the treatment of inflammatory diseases. J. Med. Chem. 62(14), 6482-6494 (2019).