LMT-28 is an orally active and the first synthetic IL-6 inhibitor that functions through direct binding to gp130. LMT-28 shows low toxicity and selectively inhibits IL-6-induced phosphorylation of STAT3, JAK2, and gp130[1].
LMT-28 reduces IL-6-induced luciferase activity by ~90% at a concentration of 50 μM and exhibits an IC50 value of 5.9 μM. LMT-28 (1-10 μM; 72 hours) inhibits IL-6-induced proliferation of the human erythroleukemic cell line TF-1[1].
LMT-28 (1-100 μM; 1 hour) selectively inhibits IL-6-induced phosphorylation of STAT3, JAK2, and gp130[1].
LMT-28 (0-0.5 mg/kg; p.o.; once daily for 15 days) alleviates CIA in mice[1].
LMT-28 (0.25 or 1 mg/kg; p.o.) ameliorates the progression of pancreatitis in mice. LMT-28 binds directly and specifically to gp130, and thereby inhibits the interaction of gp130 with the IL-6/IL-6Rα complex[1].
Reference:
[1]. Hong SS, et al. A Novel Small-Molecule Inhibitor Targeting the IL-6 Receptor β Subunit, Glycoprotein 130. J Immunol. 2015 Jul 1;195(1):237-45.