TRIM47 Inhibitors
Chemical inhibitors of TRIM47 function primarily by disrupting the ubiquitin-proteasome pathway, where TRIM47 plays a crucial role in tagging proteins for degradation. Proteasome inhibitors such as Velcade, MG132, Lactacystin, Epoxomicin, Carfilzomib, and Oprozomib directly target the proteasome complex, which is responsible for degrading ubiquitinated proteins. By binding to the proteasome, these inhibitors prevent the breakdown of proteins that TRIM47 has marked for destruction. This leads to the accumulation of these proteins within the cell. For instance, Velcade reversibly binds to the proteasome, while Lactacystin forms an irreversible bond, each achieving a similar end of inhibiting the degradation process. Carfilzomib also irreversibly binds to the proteasome, offering a prolonged inhibitory effect compared to reversible inhibitors. Similarly, Epoxomicin selectively inhibits the proteasome's chymotrypsin-like activity. These inhibitors, by halting the proteolytic function of the proteasome, accumulate ubiquitinated proteins, effectively inhibiting the regulatory role of TRIM47.
In contrast, Nelfinavir and Withaferin A, while also impacting the ubiquitin-proteasome system, do so by different mechanisms. Nelfinavir interacts with the proteasome but is primarily recognized for its activity in other areas of cellular function. Withaferin A, a steroidal lactone, is another inhibitor of the proteasome, resulting in the buildup of ubiquitinated proteins, similar to the previously mentioned chemicals. On another front, Chloroquine and Concanamycin A target the lysosomal degradation pathway. Chloroquine increases lysosomal pH, thereby affecting the environment required for the degradation of proteins that TRIM47 targets. Concanamycin A inhibits the V-ATPase that is essential for lysosomal acidification, crucial for the lysosomal breakdown process. Furthermore, MLN4924 targets the neddylation process, which is vital for the proper functioning of TRIM47 as an E3 ubiquitin ligase. By inhibiting the NEDD8-activating enzyme, MLN4924 disrupts TRIM47's ability to ubiquitinate substrates, thereby impeding its function. Lastly, Exemestane alters protein levels by affecting hormone pathways, leading to reduced availability of TRIM47 substrates for ubiquitination and subsequent degradation.
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Bortezomib | 179324-69-7 | sc-217785 sc-217785A | 2.5 mg 25 mg | $135.00 $1085.00 | 115 | |
Velcade (Bortezomib) inhibits the 26S proteasome, a complex that degrades ubiquitinated proteins. Since TRIM47 has E3 ubiquitin ligase activity, Velcade can inhibit the degradation of proteins ubiquitinated by TRIM47, leading to the accumulation of these proteins and functional inhibition of TRIM47. | ||||||
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 | |
MG132 is a proteasome inhibitor that prevents the breakdown of proteins tagged for degradation by ubiquitin, which TRIM47 as an E3 ligase is responsible for tagging. This inhibition can lead to a buildup of ubiquitinated proteins, thus functionally inhibiting the regulatory role of TRIM47. | ||||||
Lactacystin | 133343-34-7 | sc-3575 sc-3575A | 200 µg 1 mg | $188.00 $575.00 | 60 | |
Lactacystin specifically inhibits the proteasomal degradation pathway by irreversibly binding to the proteasome's catalytic β-subunit. This action blocks the degradation of proteins ubiquitinated by TRIM47, thereby functionally inhibiting TRIM47’s role in protein turnover. | ||||||
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 proteasome inhibitor that covalently binds to and inhibits the chymotrypsin-like activity of the proteasome, leading to the accumulation of TRIM47-ubiquitinated proteins, indirectly inhibiting its function by preventing substrate proteolysis. | ||||||
Carfilzomib | 868540-17-4 | sc-396755 | 5 mg | $41.00 | ||
Carfilzomib irreversibly inhibits the proteasome, thereby blocking the degradation of proteins ubiquitinated by TRIM47. This leads to the functional inhibition of TRIM47 by causing an accumulation of its substrates, which are not properly degraded. | ||||||
Oprozomib | 935888-69-0 | sc-477447 | 2.5 mg | $280.00 | ||
Oprozomib, an oral proteasome inhibitor, impedes the activity of the proteasome, leading to an accumulation of proteins tagged by TRIM47 for degradation. This functional inhibition results in disrupted protein homeostasis and interference with TRIM47's normal function. | ||||||
Nelfinavir | 159989-64-7 | sc-507314 | 10 mg | $168.00 | ||
Nelfinavir, while known as an antiretroviral medication, also inhibits the proteasome. This can indirectly inhibit TRIM47 by leading to the accumulation of proteins that it has ubiquitinated, preventing their normal degradation and thereby functionally inhibiting TRIM47's activity. | ||||||
Chloroquine | 54-05-7 | sc-507304 | 250 mg | $69.00 | 2 | |
Chloroquine functions as a lysosomotropic agent, raising the pH in lysosomes. By doing so, it can disrupt the lysosomal degradation of proteins that TRIM47 targets for degradation, resulting in an indirect functional inhibition of TRIM47 by preventing the normal breakdown of its substrates. | ||||||
Concanamycin A | 80890-47-7 | sc-202111 sc-202111A sc-202111B sc-202111C | 50 µg 200 µg 1 mg 5 mg | $66.00 $167.00 $673.00 $2601.00 | 109 | |
Concanamycin A is a V-ATPase inhibitor that disrupts lysosomal acidification, which is essential for protein degradation in lysosomes. This can hinder the degradation of proteins targeted by TRIM47, leading to functional inhibition of TRIM47 by impacting the lysosomal degradation pathway. | ||||||
MLN 4924 | 905579-51-3 | sc-484814 | 1 mg | $286.00 | 1 | |
MLN4924 inhibits the NEDD8-activating enzyme necessary for the neddylation process. Neddylation modifies certain proteins, including E3 ubiquitin ligases like TRIM47. Inhibition by MLN4924 would therefore disrupt the function of TRIM47 by impairing its ability to ubiquitinate substrates. | ||||||