KLHL26 inhibitors are a group of compounds that can indirectly suppress the activity of the KLHL26 protein through various cellular mechanisms on which KLHL26 depends for its function. In the case of compounds such as Alsterpaullone, which targets cyclin-dependent kinases, the inhibition of these kinases may lead to a reduction in the phosphorylation of proteins that are potential substrates of KLHL26.
Since phosphorylation often serves as a tag for subsequent ubiquitination, the lack of this modification might affect the ability of KLHL26 to recognize and tag these substrates for degradation. Similarly, U0126 works by inhibiting MEK1/2, which in turn prevents the activation of the ERK pathway. The ERK pathway is implicated in the phosphorylation of numerous proteins, and its inhibition could therefore interfere with the proper phosphorylation and subsequent ubiquitination of KLHL26's substrates. This disruption in the phosphorylation process would result in diminished ubiquitination activity of KLHL26, influencing various cellular processes due to the altered degradation of its substrates.