EBI2/GPR183 Antagonist

SAE-14 (compound SAE-14) is a potent, specific GPR183 antagonist with an IC₅₀ value of 28.5 nM, can antagonize 7α, 25-OHC–induced calcium mobilization with IC₅₀ value below 50 nM in HL-60 cells. GPR183 antagonist-1 can reverse allodynia in mice.

ML401, a potent chemical probe, selectively antagonizes EBI2 (also known as GPR183) with an IC₅₀ of 1.03 nM. ML401 displays activity in a chemotaxis assay (IC₅₀=6.24 nM). ML401 shows good stability and no toxicity.

GPR183 antagonist-3 (compound 33) is an oral active GPR183 antagonist with the IC₅₀ of 8.7 μM. GPR183 antagonist-3 displays strong in vitro antimigration and anti-inflammatory activity in monocytes, and improves the pathological symptoms of DSS-induced experimental colitis.

GPR183 antagonist-4 is a potent and selective GPR183 antagonist with an IC₅₀ of 8.31 nM. GPR183 antagonist-4 inhibits receptor activation-mediated calcium signaling by antagonizing GPR183, and exhibits efficacy in ameliorating neuropathic pain-related allodynia. GPR183 antagonist-4 is useful for research on GPR183 signaling and neuropathic pain.