K67

K67 is a selective the interaction between Keap1 and S349 phosphorylated p62 inhibitor, with an IC₅₀ of 1.5 μM. K67 has a weaker inhibitory effect on the interaction between Keap1 and Nrf2 (IC₅₀ is 6.2 μM). K67 competitively binds to the binding site of Keap1 with p-p62, blocking the abnormal activation of the p62-dependent Nrf2 pathway. K67 inhibits tumor cell proliferation and enhances the sensitivity of hepatocellular carcinoma (HCC) to chemotherapeutic drugs by restoring Keap1-mediated ubiquitination and degradation of Nrf2^[1][2]. In Vitro: K67 (50 μM; 24-72 h) significantly inhibits the proliferation of Huh1 cells and Huh7 cells expressing phospho-mimetic p62 in cell viability assays¹.
K67 (50 μM; 12-48 h) inhibits the expression of Nrf2 target genes in Huh1 cells¹.
K67 (50 μM; 4-36 h respectively) significantly reduces the content of Nrf2 in the nucleus and cytoplasm of Huh1 cells and Keap1 accumulates in a time-dependent manner¹.
K67 (50 μM; treated for 12 h) significantly inhibits the interaction between phosphorylated p62 and Keap1 and promotes the interaction between Nrf2 and Keap1 in immunoprecipitation assays in Huh1 cells¹.
K67 (50 μM; treated for 4 h + 8 h (with the addition of the proteasome inhibitor lactacystin)) significantly promotes the ubiquitination of Nrf2 in Huh7 cells (expressing S351E)¹.