SIAH-1B Inhibitors
Chemical inhibitors of SIAH-1B exploit various molecular mechanisms to impede its function in the ubiquitin-proteasome system. P22077 directly targets SIAH-1B's ubiquitin ligase activity, preventing it from tagging substrates for degradation, leading to an accumulation of these proteins. Similarly, MLN4924 disrupts SIAH-1B activity but does so by inhibiting the neddylation of cullin proteins, which are essential for the E3 ubiquitin ligase function of SIAH-1B, resulting in a broader inactivation of the ligase complex. Ginkgolic Acid, on the other hand, impairs the SUMOylation process. Since SIAH-1B is known to have substrate specificity for SUMO-conjugated proteins, this disruption can indirectly limit SIAH-1B's ability to recognize and process its substrates. Withaferin A and MG132 both target the proteasome, the downstream effect of SIAH-1B's activity. By inhibiting the proteasome, these chemicals lead to the build-up of ubiquitinated proteins, effectively halting the degradation process that SIAH-1B facilitates.
Other inhibitors such as Curcumin and Chloroquine employ different methods to interfere with SIAH-1B's role. Curcumin reduces the ubiquitination of substrates by inhibiting various E3 ubiquitin ligases, including SIAH-1B. In contrast, Chloroquine's mode of action involves raising the pH in acidic vesicles, which can disrupt multiple protein degradation pathways, not just the one mediated by SIAH-1B. Bortezomib, another proteasome inhibitor, prevents the breakdown of proteins tagged by SIAH-1B, echoing the effects of Withaferin A and MG132. EerI affects the ERAD pathway where SIAH-1B operates, leading to the stabilization of proteins that would otherwise be degraded. Betulin and Embelin impact the ubiquitin-proteasome system indirectly; Betulin by modulating the NF-kB pathway and Embelin by inhibiting XIAP, both of which can affect the regulation of SIAH-1B's targets. Lastly, NSC 66811 disrupts the interaction between E3 ubiquitin-protein ligases and their substrates, thereby influencing SIAH-1B's ability to ubiquitinate and target proteins for degradation. Each of these chemicals, through their distinct mechanisms, serves to inhibit the functional activity of SIAH-1B within the cellular environment.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
P22077 | 1247819-59-5 | sc-478536 | 10 mg | $162.00 | ||
P22077 is a small molecule known to inhibit the activity of SIAH-1B by blocking its ubiquitin ligase activity, leading to the accumulation of its substrates and preventing their degradation. This results in functional inhibition of SIAH-1B's role in targeting proteins for proteasomal degradation. | ||||||
MLN 4924 | 905579-51-3 | sc-484814 | 1 mg | $280.00 | 1 | |
MLN4924 inhibits SIAH-1B indirectly by preventing the neddylation of cullin proteins, which are necessary for the cullin-RING ligases (CRLs) to which SIAH-1B belongs. This leads to inactivation of the E3 ubiquitin ligase activity of SIAH-1B, inhibiting its function. | ||||||
Withaferin A | 5119-48-2 | sc-200381 sc-200381A sc-200381B sc-200381C | 1 mg 10 mg 100 mg 1 g | $127.00 $572.00 $4090.00 $20104.00 | 20 | |
Withaferin A is known to disrupt the function of proteasomes. Given that SIAH-1B's function is to tag proteins for proteasomal degradation, inhibiting the proteasome can indirectly inhibit the functional consequence of SIAH-1B activity by preventing the degradation of its substrates. | ||||||
Curcumin | 458-37-7 | sc-200509 sc-200509A sc-200509B sc-200509C sc-200509D sc-200509F sc-200509E | 1 g 5 g 25 g 100 g 250 g 1 kg 2.5 kg | $36.00 $68.00 $107.00 $214.00 $234.00 $862.00 $1968.00 | 47 | |
Curcumin has been reported to inhibit the activity of several E3 ubiquitin ligases. By inhibiting the E3 ligase activity, Curcumin can decrease the ubiquitination of substrates of SIAH-1B, thereby inhibiting its function. | ||||||
Chloroquine | 54-05-7 | sc-507304 | 250 mg | $68.00 | 2 | |
Chloroquine raises the pH of acidic vesicles, such as lysosomes and endosomes, which can result in the inhibition of protein degradation pathways. Since SIAH-1B is involved in the proteasomal degradation pathway, Chloroquine can indirectly inhibit SIAH-1B function by disrupting protein degradation. | ||||||
MG-132 [Z-Leu- Leu-Leu-CHO] | 133407-82-6 | sc-201270 sc-201270A sc-201270B | 5 mg 25 mg 100 mg | $56.00 $260.00 $980.00 | 163 | |
MG132 is a proteasome inhibitor that prevents the degradation of ubiquitin-conjugated proteins. By inhibiting the proteasome, MG132 can indirectly inhibit SIAH-1B by preventing the degradation of its ubiquitinated substrates, thus inhibiting its function. | ||||||
Bortezomib | 179324-69-7 | sc-217785 sc-217785A | 2.5 mg 25 mg | $132.00 $1064.00 | 115 | |
Bortezomib is another proteasome inhibitor that can indirectly inhibit the function of SIAH-1B by preventing the proteasomal degradation of proteins that SIAH-1B targets for ubiquitination, thereby inhibiting its functional role in protein turnover. | ||||||
Betulin | 473-98-3 | sc-234016 | 1 g | $102.00 | 5 | |
Betulin has been shown to interfere with the NF-kB pathway, which is involved in the regulation of various cellular processes including ubiquitination. By inhibiting this pathway, Betulin can indirectly inhibit SIAH-1B by affecting the regulation of proteins that SIAH-1B would target for degradation. | ||||||
Embelin | 550-24-3 | sc-201555 sc-201555A | 10 mg 50 mg | $87.00 $332.00 | 5 | |
Embelin is a small molecule that inhibits the X-linked inhibitor of apoptosis protein (XIAP), which is a member of the IAP family that also modulates ubiquitin ligases. By inhibiting XIAP, Embelin can indirectly inhibit SIAH-1B by affecting the ubiquitination and degradation pathways that SIAH-1B is involved in. | ||||||
C646 | 328968-36-1 | sc-364452 sc-364452A | 10 mg 50 mg | $260.00 $925.00 | 5 | |
NSC 66811 disrupts the interaction between the E3 ubiquitin-protein ligase and its substrate proteins. By doing so, it indirectly inhibits SIAH-1B by blocking its ability to ubiquitinate substrates, thereby inhibiting its function in the ubiquitin-proteasome pathway. | ||||||