KEAP1 and familial pancreatic carcinoma: In order to detect whether esculetin affects the regulation of the antioxidant reaction elements pathway, Arora treated pancreatic cancer cells with esculetin and detected the interaction between Nrf2 and KEAP1, and found that esculetin could directly bind to KEAP1, then destroying the interaction of Nrf2-KEAP1, releasing Nrf2 from the inhibition of KEAP1, increasing the amount of phosphorylation of Nrf2 in cells and increasing the expression of NAD(P)H quinone oxidoreductase-1 (NQO1), the direct target of Nrf2 (28).