RNF166 Inhibitors
Chemical inhibitors of RNF166 target the proteasome, a complex that degrades ubiquitinated proteins, which is a key process that RNF166 is involved in. The peptide aldehyde MG-132, lactacystin, and the selective irreversible inhibitor epoxomicin all function by binding to the catalytic sites of the proteasome, thereby preventing the breakdown of proteins marked for degradation. RNF166 functions as an E3 ubiquitin-protein ligase, tagging proteins with ubiquitin to signal for their degradation by the proteasome. When these inhibitors are applied, the proteasome's ability to degrade ubiquitinated proteins is compromised, leading to an accumulation of these proteins within the cell. This accumulation effectively inhibits the function of RNF166 by overwhelming the enzyme with substrates, which may lead to a feedback inhibition or depletion of available ubiquitin, thereby halting further activity of RNF166.
Other proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib, also exhibit inhibition of RNF166 through similar mechanisms. Bortezomib, a boronic acid dipeptide, and carfilzomib, an epoxyketone-based molecule, both act to block the 26S proteasome, whereas ixazomib preferentially binds to the beta5 subunit of the 20S proteasome. Oprozomib, delanzomib, and marizomib are additional proteasome inhibitors that can indirectly inhibit RNF166 by preventing the degradation of its ubiquitinated targets. This causes an indirect inhibition of RNF166's ligase activity as it is unable to process the excess of substrates due to the inhibited proteasomal activity. Nelfinavir, although initially developed as an HIV protease inhibitor, has been shown to inhibit the proteasome, thus leading to an increase in ubiquitinated protein levels and indirectly inhibiting RNF166 by saturating the protein with its substrates. All these inhibitors share a common outcome: they raise the levels of ubiquitinated proteins within the cell, which indirectly inhibits RNF166 by impacting its substrate handling capacity.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
MG-132 [Z-Leu- Leu-Leu-CHO] | 133407-82-6 | sc-201270 sc-201270A sc-201270B | 5 mg 25 mg 100 mg | $60.00 $265.00 $1000.00 | 163 | |
MG-132 is a peptide aldehyde that inhibits proteasomes, which are crucial for protein degradation. RNF166 is known to be involved in ubiquitin-protein ligase activity which tags proteins for degradation. Inhibition of the proteasome by MG-132 would lead to the accumulation of ubiquitinated proteins, thus potentially inhibiting the function of RNF166 by overwhelming it with substrates. | ||||||
Lactacystin | 133343-34-7 | sc-3575 sc-3575A | 200 µg 1 mg | $188.00 $575.00 | 60 | |
Lactacystin is an irreversible proteasome inhibitor that binds specifically to the catalytic β-subunit of the proteasome. By inhibiting the proteasome, it prevents the degradation of proteins ubiquitinated by RNF166, causing an inhibition of RNF166 function due to substrate accumulation. | ||||||
Epoxomicin | 134381-21-8 | sc-201298C sc-201298 sc-201298A sc-201298B | 50 µg 100 µg 250 µg 500 µg | $137.00 $219.00 $449.00 $506.00 | 19 | |
Epoxomicin is a selective, irreversible proteasome inhibitor. It covalently binds to the active site of the proteasome, leading to an accumulation of proteins targeted by RNF166 for ubiquitination and subsequent degradation, thus inhibiting the functional activity of RNF166. | ||||||
Bortezomib | 179324-69-7 | sc-217785 sc-217785A | 2.5 mg 25 mg | $135.00 $1085.00 | 115 | |
Bortezomib is a boronic acid dipeptide that inhibits the 26S proteasome. By blocking proteasomal activity, Bortezomib indirectly inhibits RNF166's role in the degradation of ubiquitinated proteins by causing a backlog of these proteins. | ||||||
Carfilzomib | 868540-17-4 | sc-396755 | 5 mg | $41.00 | ||
Carfilzomib is an epoxyketone-based proteasome inhibitor that irreversibly binds to and inhibits the proteasome. This inhibition disrupts the turnover of proteins ubiquitinated by RNF166, leading to an indirect inhibition of RNF166’s function. | ||||||
Ixazomib | 1072833-77-2 | sc-489103 sc-489103A | 10 mg 50 mg | $311.00 $719.00 | ||
Ixazomib is a small-molecule proteasome inhibitor. It preferentially binds to and inhibits the β5 subunit of the 20S proteasome, which can result in the inhibition of RNF166's ability to facilitate the degradation of its ubiquitinated protein targets. | ||||||
Oprozomib | 935888-69-0 | sc-477447 | 2.5 mg | $280.00 | ||
Oprozomib, an oral proteasome inhibitor, acts on the proteasome to prevent the degradation of ubiquitinated proteins. This leads to an indirect inhibition of the enzymatic activity of RNF166 by preventing the clearance of its substrates. | ||||||
Delanzomib, free base | 847499-27-8 | sc-396774 sc-396774A | 5 mg 10 mg | $160.00 $300.00 | ||
Delanzomib is a proteasome inhibitor that targets and binds to the 20S core particle of the proteasome. This action can inhibit the function of RNF166 by causing the accumulation of ubiquitinated proteins, which are RNF166's substrates. | ||||||
Nelfinavir | 159989-64-7 | sc-507314 | 10 mg | $168.00 | ||
Nelfinavir is known as an HIV protease inhibitor, but it also inhibits the proteasome. This inhibition can lead to an accumulation of ubiquitinated substrates, indirectly inhibiting the ligase activity of RNF166 by substrate competition. | ||||||