FBXW10 Inhibitors

FBXW10 inhibitors encompass a range of chemicals that indirectly impact the activity of FBXW10 by targeting different elements of the ubiquitin-proteasome system (UPS) and associated cellular signaling pathways. Proteasome inhibitors such as MG132, Bortezomib, Lactacystin, Velcade, Epoxomicin, and Withaferin A function by directly inhibiting the proteasome's ability to degrade ubiquitinated proteins. This leads to the accumulation of proteins marked for degradation by FBXW10, effectively reducing the turnover of these substrates and diminishing the functional impact of FBXW10 in cellular processes.

Additional inhibitors act on various upstream components of the UPS or related pathways. For instance, MLN4924 disrupts the neddylation process that is crucial for the activation of cullin proteins within the SCF complex, thus potentially decreasing the ubiquitination activity of FBXW10. PYR-41 targets the ubiquitin-activating enzyme E1, which is essential for the initial step of ubiquitin conjugation to substrates, thereby reducing the overall ubiquitination including those mediated by FBXW10. Compounds like LiCl and Nutlin-3 target signaling pathways that indirectly modulate the activity of E3 ubiquitin ligases like FBXW10. LiCl inhibits GSK-3β, a kinase that can modify the phosphorylation status of FBXW10 substrates and influence their recognition and ubiquitination by the SCF complex. Nutlin-3 stabilizes p53 by inhibiting MDM2, which may lead to altered expression of genes that encode FBXW10 or its substrates, thereby affecting the functional role of FBXW10 in the cell. Lastly, inhibitors such as Chloroquine and ALLN affect the cellular degradation machinery by increasing lysosomal pH and inhibiting other proteases like calpains, respectively. These actions can lead to a reduced degradation of FBXW10 substrates, again indirectly influencing the activity of FBXW10.