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CU-CPT8m is an antagonist of toll-like receptor 8 (TLR8; Kd = 220 nM; IC50 = 67 nM in a reporter assay). It is selective for TLR8 over a panel of all other human TLRs when used at a concentration of 1 μM. CU-CPT8m (1 μM) inhibits increases in TNF-α and IL-8 mRNA expression induced by the TLR8 agonist R-848 in TLR8-overexpressing HEK-Blue cells. It also inhibits R-848-induced increases in TNF-α protein levels in differentiated THP-1 monocytes and human primary peripheral blood mononuclear cells (PBMCs) in a concentration-dependent manner. CU-CPT8m decreases TNF-α and IL-8 levels in synovial cells derived from patients with osteoarthritis and TNF-α levels in PBMCs derived from patients with rheumatoid arthritis..
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