KLHL10 Inhibitors

KLHL10 inhibitors are small molecules designed to target and interfere with the activity of the KLHL10 protein. KLHL10, or Kelch-like family member 10, is part of the larger Kelch-like protein family, characterized by their highly conserved BTB (Bric-a-brac, Tramtrack, Broad Complex) domain, which mediates protein-protein interactions. Additionally, these proteins contain Kelch repeats that form a β-propeller structure, facilitating substrate recognition. KLHL10 is known to function as an adaptor protein within E3 ubiquitin ligase complexes, where it aids in the ubiquitination and subsequent degradation of specific substrates, a key regulatory process for maintaining protein homeostasis. Inhibitors of KLHL10 typically work by binding to this protein, obstructing its interactions within the ubiquitin-proteasome system.

These inhibitors are developed using diverse chemistries, with molecular scaffolds that can interfere with the protein's substrate recognition or its dimerization ability. Structurally, these compounds are optimized to interact with the BTB domain or the Kelch repeats, disrupting the formation of functional complexes necessary for ubiquitination. Many of these inhibitors exhibit specificity by targeting the precise interfaces responsible for KLHL10's protein-protein interactions, avoiding broader effects on other Kelch-like proteins. The design and modification of KLHL10 inhibitors rely heavily on structural biology and computational modeling to refine interactions with the protein's active sites. This high level of specificity allows for a detailed understanding of the role KLHL10 plays in various biological processes. KLHL10 inhibitors are valuable molecular tools in studying the regulation of ubiquitination pathways and protein degradation.