Takinib

Uses

Takinib has been used as an inhibitor of transforming 28 growth factor - β-activated kinase -1 (TAK-1) in human leukemia monocytic THP-1 cells. It may be used as a TAK1 inhibitor in Jurk at cells.

Biological Activity

Takinib is a selective inhibitor of TAK1/MAP3K7 kinase, which is a member of the MAP3K family and a key regulator of cell death. It binds in the TAk1 ATPbinding pocket with an IC50 value of 9.5 nM. Takinib selectively induced apoptosis following TNF-α stimulation in rheumatoid arthritis and breast cancer.

in vivo

IC 50

TAK1: 9.5 nM (IC₅₀); IRAK4: 120 nM (IC₅₀); IRAK1: 390 nM (IC₅₀); GCK: 430 nM (IC₅₀); CLK2: 430 nM (IC₅₀); MINK1: 1.9 μM (IC₅₀)

storage

Store at -20°C

Background

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 over other targets. The inhibitor Takinib induces apoptosis following TNF-α stimulation in cell models of rheumatoid arthritis and metastatic breast cancer. 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. 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.

References

[1] Totzke, J. et al. (2017) Cell Chem Biol 24, 1029-1039.e7.
[2] Scarneo, S.A. et al. (2020) Oncotarget 11, 1961-1970.
[3] Panipinto, P.M. et al. (2021) Int J Mol Sci 22, 12580. doi: 10.3390/ijms222212580.