HS-276

HS-276 is a TGF-beta-activated kinase 1 (TAK1) inhibitor (IC50 = 8. nM). It is selective for TAK1 over a panel of 137 other kinases at 10 µM but does inhibit CDC-like kinase 2 (Clk2), hexokinase (HK), and unc-51-like autophagy activating kinase 2 (ULK2, IC50s = 29, 33, and 63 nM, respectively). HS-276 inhibits LPS-induced increases in secretion of TNF, IL-6, and IL-1beta from THP-1 macrophages differentiated by phorbol 12-myristate 13-acetate (PMA, IC50s = 138, 201, and 234 nM, respectively). It inhibits collagen-induced increases in pannus formation, cartilage damage, bone resorption, and periosteal bone formation in a mouse model of rheumatoid arthritis when administered at a dose of 50 mg/kg twice per day.. Solulibility: DMSO: Sparingly soluble: 1-10 mg/ml: .