FBXO39 Inhibitors

FBXO39 proteasome inhibitors such as MG132, Bortezomib, Lactacystin, Epoxomicin, Clasto-lactacystin beta-lactone, Marizomib, Oprozomib, and Carfilzomib function by causing polyubiquitinated proteins to accumulate. This accumulation results from the blockade of the proteasome's proteolytic activity, which may stabilize FBXO39's substrate proteins and thereby affect the protein's regulatory roles. These compounds are particularly effective in revealing the dynamics of protein turnover and the intricate pathways of cellular protein regulation. Other inhibitors like Pyr-41 and MLN4924 (Pevonedistat) act on the processes that precede protein ubiquitination. Pyr-41 inhibits the ubiquitin-activating enzyme E1, crucial for the ubiquitin conjugation to substrates, whereas MLN4924 impedes the NEDD8-activating enzyme, affecting the function of cullin-RING ubiquitin ligases, which are part of the ubiquitin ligase complexes that FBXO39 could be associated with. This disruption in the ubiquitination and neddylation processes can significantly alter FBXO39's ability to mediate protein turnover within the cell. Inhibitors targeting deubiquitinating enzymes, such as IU1 and VLX1570, restrict the recycling of ubiquitin and the removal of ubiquitin from proteins destined for degradation. By inhibiting USP14 and proteasome-associated deubiquitinases, these compounds affect the balance of protein ubiquitination and deubiquitination that governs the fate of FBXO39's potential substrates.