IL-6

LMT-28 (0-0.5 mg/kg; p.o.; once daily for 15 days) alleviates CIA in mice. 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. Animal Model: Six-week-old male DBA/1J mice (collagen-induced arthritis mice, CIA) Dosage: 0-0.5 mg/kg Administration: Oral; once daily for 15 days Result: Markedly reduced the serum levels of cartilage oligomeric matrix protein (COMP) by 50%, serum amyloid P (SAP) by 55%, and anti-CII IgG by 62%.

LMT-28 reduces IL-6-induced luciferase activity by ~90% at a concentration of 50 μM and exhibits an IC 50 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. LMT-28 (1-100 μM; 1 hour) selectively inhibits IL-6-induced phosphorylation of STAT3, JAK2, and gp130. Cell Proliferation Assay Cell Line: TF-1 cells (1 ng/mL IL-6-induced) Concentration: 1, 10, 100, 1000, 10000 nM Incubation Time: 72 hours Result: Markedly inhibited IL-6–induced TF-1 proliferation with an IC50 value of 7.5 μM. Western Blot Analysis Cell Line: HepG2 cells (treated with 10 ng/mL IL-6) Concentration: 1, 3, 10, 30, and 100 μM Incubation Time: 1 hour Result: Inhibits IL-6-induced phosphorylation of STAT3, JAK2, and gp130.

LMT-28 是一种具有口服活性的通过直接与 gp130 结合而发挥作用的 IL-6 抑制剂。LMT-28 具有低毒性，并选择性抑制 IL-6 诱导的 STAT3、JAK2 和 gp130 的磷酸化。