HECTD4 Inhibitors
HECTD4 inhibitors are a diverse group of chemical compounds that influence the ubiquitin-proteasome system, impacting the functional activity of HECTD4, an E3 ubiquitin-protein ligase. Compounds like MG132, Lactacystin, and Epoxomicin function as proteasome inhibitors and prevent the degradation of proteins tagged for destruction, leading to an accumulation of polyubiquitinated substrates. This accumulation indirectly inhibits HECTD4 by overwhelming the degradation machinery that HECTD4 feeds into, thus diminishing the requirement for its ligase activity. On a similar note, compounds such as Clasto-Lactacystin β-lactone, Bortezomib (also known as Velcade), Carfilzomib, Ixazomib, and Oprozomib, all act to inhibit the 26S proteasome, thereby stalling the proteolytic turnover of proteins that HECTD4 helps to ubiquitinate. The result is a functional suppression of HECTD4's role in protein degradation pathways.
Moreover, chemical compounds like MLN4924 and PYR-41 take an upstream approach by inhibiting enzymes crucial for the ubiquitination process itself. MLN4924 inhibits the NEDD8 activating enzyme, which is necessary for the functional activation of cullin proteins that are part of E3 ubiquitin ligase complexes, potentially affecting the spectrum of HECTD4's activity. PYR-41 targets the ubiquitin-activating enzyme E1, halting the ubiquitination cascade at its very beginning and thus indirectly reducing the ubiquitin ligase function of HECTD4. Lastly, NMS-873 inhibits the p97/VCP ATPase, disrupting the extraction and delivery of ubiquitinated proteins to the proteasome, which further influences the functional demand on HECTD4 by perturbing the downstream effects of its ligase activity. Collectively, these inhibitors demonstrate the intricate interplay between HECTD4's ligase activity and the broader ubiquitin-proteasome system, illustrating the indirect yet significant impact these compounds have on HECTD4's biological function.
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 | |
This is a proteasome inhibitor that prevents the degradation of proteins by the ubiquitin-proteasome system. Since HECTD4 is an E3 ubiquitin-protein ligase, MG132 can indirectly inhibit HECTD4 by accumulating ubiquitinated proteins, thereby saturating the system HECTD4 is part of and reducing its functional activity. | ||||||
Lactacystin | 133343-34-7 | sc-3575 sc-3575A | 200 µg 1 mg | $188.00 $575.00 | 60 | |
Lactacystin is another proteasome inhibitor that irreversibly binds to and inhibits the 20S proteasome. By blocking proteasomal activity, it indirectly affects HECTD4 function, as the ligase activity of HECTD4 is rendered less effective when proteins are not properly degraded. | ||||||
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 | |
This compound is a selective proteasome inhibitor that covalently binds to the active site of the proteasome. Its action leads to an accumulation of ubiquitinated proteins and a consequent indirect inhibition of HECTD4 by reducing the demand for its E3 ligase activity. | ||||||
MLN 4924 | 905579-51-3 | sc-484814 | 1 mg | $286.00 | 1 | |
MLN4924 is an inhibitor of NEDD8 activating enzyme (NAE), which is essential for the neddylation of cullin proteins involved in ubiquitin ligase activity. By inhibiting NAE, MLN4924 indirectly inhibits cullin RING E3 ubiquitin ligases, potentially reducing the functional activity of HECTD4 as part of the ubiquitin-proteasome pathway. | ||||||
Ubiquitin E1 Inhibitor, PYR-41 | 418805-02-4 | sc-358737 | 25 mg | $360.00 | 4 | |
PYR-41 is a cell-permeable inhibitor of ubiquitin-activating enzyme E1. It inhibits the initial step of the ubiquitination cascade, thereby indirectly diminishing HECTD4's activity in the ubiquitination process. | ||||||
Bortezomib | 179324-69-7 | sc-217785 sc-217785A | 2.5 mg 25 mg | $135.00 $1085.00 | 115 | |
Bortezomib is a dipeptide boronic acid analog that reversibly inhibits the 26S proteasome. | ||||||
Carfilzomib | 868540-17-4 | sc-396755 | 5 mg | $41.00 | ||
Carfilzomib is an irreversible proteasome inhibitor that has a similar effect as Bortezomib, leading to the accumulation of ubiquitinated proteins and indirectly inhibiting the functional activity of HECTD4. | ||||||
Ixazomib | 1072833-77-2 | sc-489103 sc-489103A | 10 mg 50 mg | $311.00 $719.00 | ||
A reversible proteasome inhibitor that acts similarly to Bortezomib and Carfilzomib, Ixazomib results in the accumulation of ubiquitinated substrates, reducing the functional demand on HECTD4. | ||||||
Oprozomib | 935888-69-0 | sc-477447 | 2.5 mg | $280.00 | ||
Oprozomib is an oral proteasome inhibitor, which, like the other proteasome inhibitors mentioned, indirectly reduces HECTD4 activity through the accumulation of polyubiquitinated proteins. | ||||||
NMS-873 | 1418013-75-8 | sc-478803 | 5 mg | $300.00 | ||
NMS-873 is a p97/VCP ATPase inhibitor, which can indirectly inhibit HECTD4 by disrupting the processing of ubiquitinated proteins that rely on the p97/VCP complex for delivery to the proteasome, therefore affecting the cellular need for HECTD4's ubiquitin ligase activity. | ||||||