Takinib #64030

Takinib is a potent and selective small molecule inhibitor of TAK1, a MAP3K family protein and important moderator of cell survival and death in TNF-α signaling. Takinib preferentially binds and inhibits TAK1 (IC50 of 9.5 nM) over other targets (e.g., IRAK4: IC₅₀ of 120 nM and IRAK1: IC₅₀ of 390 nM). The inhibitor Takinib induces apoptosis following TNF-α stimulation in cell models of rheumatoid arthritis and metastatic breast cancer (1). Inhibition of TAK1 by Takinib resulted in increased cell death in several cancer cell lines, and reduced pro-inflammatory and pro-angiogenic signaling in tumor-associated macrophages, suggesting that Takinib regulation of TAK1 may be a beneficial therapeutic strategy (2). Additional evidence suggests that Takinib inhibition of cytokine production may also work along additional pathways, including the JAK/STAT pathway. In a study examining inflammation in human rheumatoid arthritis synovial fibroblasts, treatment with Takinib results in specifically reduced IL-1β-induced STAT3 phosphorylation, nuclear translocation, and DNA binding (3).