| References: |
At 10 mM, Takinib shows significant inhibitory activity (<10% enzyme activity after exposure) on six serine/threonine kinases, including TAK1, IRAK4, IRAK1, GCK, CLK2, and MINK1. Analysis reveals that increasing concentrations of Takinib leads to a decrease in Vmax while maintaining KM. When the enzyme is activated with 5 mM ATP for 3 hr, the same Vmax is reached for 0, 10, 50, and 100 nM Takinib, and KM increases for these concentrations, which implies that Takinib is an ATP-competitive inhibitor if TAK1 is ATP activated. Importantly, results show that Takinib inhibits the function of both activated and un-activated TAK1 with identical potency. TNF-α stimulation in the presence of Takinib induces caspase activity in MDA-MB-231 cells in a dose-dependent manner, whereas unstimulated cells do not upregulate caspase activity. Takinib reduces phosphorylation significantly but does not influence total protein levels. Takinib inhibits phosphorylation of IKK, MAPK 8/9, and c-Jun in a dose-dependent manner. Takinib shows an almost complete inhibition of IL-6 secretion at micromolar concentrations following 24 hr of treatment in the presence of TNF-α. |
