KLHL4 Inhibitors

KLHL4, embedded in the ubiquitin-proteasome system, primarily operates to tag proteins for degradation. Therefore, compounds inhibiting the proteasome – MG132, Lactacystin, ALLN, Epoxomicin, Bortezomib, and Celastrol – can cause an accumulation of ubiquitinated proteins. This accumulation may hinder KLHL4's efficiency as the cellular machinery becomes overwhelmed, thus diminishing its ability to operate optimally. IWP-2 and IWR-1, by targeting the Wnt pathway, may indirectly affect KLHL4. KLHL4 is indeed regulated or interacts with the Wnt pathway components, these inhibitors can suppress its typical functionality. On a similar trajectory, Neratinib, a tyrosine kinase inhibitor, has the potential to impact KLHL4, the protein exhibits tyrosine kinase-related functions or partnerships. Further complicating the landscape is DBeQ's inhibition of p97, a significant component in protein degradation. By disrupting this, KLHL4's role might be indirectly impeded. Similarly, Spautin-1, through its modulation of autophagy, can alter the ubiquitination landscape, which KLHL4 heavily relies on. Lastly, the introduction of Ubiquitin aldehyde brings forth a unique mechanism: the inhibition of deubiquitinating enzymes. With an uptick in ubiquitinated proteins, KLHL4 may find its targeting capacity strained.