Takinib

**Takinib** is a potent and selective small molecule inhibitor of transforming growth factor beta-activated kinase 1 (TAK1/MAP3K7), a serine/threonine kinase in the MAP3K family that mediates pro-survival signaling downstream of TNF-α and other stimuli via activation of NF-κB and MAPK pathways. It binds non-competitively in the ATP-binding pocket, slowing the rate-limiting autophosphorylation step of TAK1 activation (IC50 9.5 nM), with >1.5 log selectivity over other kinases including IRAK1/4 and GCK. Developed by researchers at Duke University, Takinib induces TNF-α-dependent apoptosis in cell models of rheumatoid arthritis (RA) fibroblast-like synoviocytes and metastatic breast cancer (MDA-MB-231), reduces pro-inflammatory cytokine secretion (e.g., TNF, IL-6) in LPS-stimulated macrophages, and shows efficacy in preclinical models of inflammation, sepsis, subarachnoid hemorrhage, and fibrosis without significant toxicity in mice up to 50 mg/kg[1][2][3][4][7].