KLHL32 Inhibitors
Chemical inhibitors of KLHL32 function through various mechanisms to impede its role in the ubiquitin-proteasome system, which is central to protein degradation in cells. Apigenin, Wortmannin, LY294002, and 3-Methyladenine target the PI3K/Akt pathway, which is crucial for the regulation of proteostasis. Apigenin acts by inhibiting the PI3K/Akt pathway, which could lead to the functional inhibition of KLHL32, possibly by preventing its substrate recognition or reducing its ubiquitin ligase activity. Wortmannin is a strong and irreversible inhibitor of PI3K, which would lead to a decrease in the phosphorylation of substrates tied to protein degradation, thereby inhibiting the functionality of KLHL32. Similarly, LY294002 is a selective inhibitor of PI3K, and its action can attenuate downstream Akt signaling, potentially leading to a decrease in the ubiquitination process KLHL32 is part of. 3-Methyladenine, known for its role in autophagy inhibition, can indirectly lead to a decrease in KLHL32's activity by reducing the demand for proteasomal degradation.
Other inhibitors such as U0126, SP600125, SB203580, MG132, Lactacystin, Bortezomib (also known as Velcade), and Carfilzomib impact KLHL32 through different nodes of the cell's signaling and degradation pathways. U0126, a selective inhibitor of MEK1/2, impedes the ERK1/2 signaling pathways which can regulate the activity of E3 ubiquitin ligases, to which KLHL32 belongs. SP600125 inhibits the JNK pathway, affecting the phosphorylation-dependent regulation of E3 ligases and thus the function of KLHL32. SB203580 specifically targets p38 MAPK, and its inhibition can affect the phosphorylation status of substrates in the ubiquitin-proteasome pathway, potentially leading to an inhibition of KLHL32's role. MG132 is a proteasome inhibitor that causes an accumulation of polyubiquitinated proteins, which can lead to feedback inhibition of KLHL32 due to substrate build-up. Lactacystin acts similarly by irreversibly binding to the proteasome's active site, preventing the turnover of ubiquitinated substrates and leading to an indirect reduction in KLHL32 activity. Bortezomib and Carfilzomib, both proteasome inhibitors, lead to a backlog of proteins destined for degradation, which can inhibit the functionality of KLHL32 by preventing the degradation of its substrates.
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Apigenin | 520-36-5 | sc-3529 sc-3529A sc-3529B sc-3529C sc-3529D sc-3529E sc-3529F | 5 mg 100 mg 1 g 5 g 25 g 100 g 1 kg | $32.00 $210.00 $720.00 $1128.00 $2302.00 $3066.00 $5106.00 | 22 | |
Apigenin inhibits the PI3K/Akt pathway, which is involved in the regulation of proteostasis, including the degradation of misfolded proteins. Since KLHL32 is associated with protein degradation through the ubiquitin-proteasome system, inhibiting PI3K/Akt can lead to the functional inhibition of KLHL32 by preventing its substrate recognition or reducing its ubiquitin ligase activity. | ||||||
Wortmannin | 19545-26-7 | sc-3505 sc-3505A sc-3505B | 1 mg 5 mg 20 mg | $66.00 $219.00 $417.00 | 97 | |
Wortmannin is a potent and irreversible inhibitor of PI3K, which is upstream of Akt signaling. Akt pathway inhibition can decrease the phosphorylation of substrates involved in protein degradation, thereby potentially inhibiting the activity of KLHL32 as it is part of the cellular quality control mechanism. | ||||||
LY 294002 | 154447-36-6 | sc-201426 sc-201426A | 5 mg 25 mg | $121.00 $392.00 | 148 | |
LY294002 is a selective inhibitor of PI3K, which can attenuate the downstream Akt signaling. By inhibiting this pathway, it can reduce the ubiquitination process that KLHL32 is part of, thus inhibiting its function in tagging proteins for degradation. | ||||||
Autophagy Inhibitor, 3-MA | 5142-23-4 | sc-205596 sc-205596A | 50 mg 500 mg | $56.00 $256.00 | 113 | |
3-Methyladenine is known to inhibit PI3K, which indirectly could lead to the inhibition of the autophagic degradation pathways. As KLHL32 is linked with proteasomal degradation, this may result in a decrease in the functional activity of KLHL32 due to a reduced demand for proteasomal degradation when autophagy is suppressed. | ||||||
U-0126 | 109511-58-2 | sc-222395 sc-222395A | 1 mg 5 mg | $63.00 $241.00 | 136 | |
U0126 is a selective inhibitor of MEK1/2 which leads to the inhibition of ERK1/2 signaling pathways. These pathways can regulate the activity of several E3 ubiquitin ligases, of which KLHL32 could be a member; thus, inhibition of MEK could suppress the functional activity of KLHL32. | ||||||
SP600125 | 129-56-6 | sc-200635 sc-200635A | 10 mg 50 mg | $40.00 $150.00 | 257 | |
SP600125 is an inhibitor of c-Jun N-terminal kinase (JNK), which can modulate the activity of various proteins through phosphorylation. Inhibiting JNK might reduce the phosphorylation-dependent regulation of E3 ubiquitin ligases, potentially inhibiting the function of KLHL32. | ||||||
SB 203580 | 152121-47-6 | sc-3533 sc-3533A | 1 mg 5 mg | $88.00 $342.00 | 284 | |
SB203580 is a specific inhibitor of p38 MAPK. By inhibiting p38 MAPK, it can affect the phosphorylation status of substrates involved in the ubiquitin-proteasome pathway, which could lead to the inhibition of KLHL32's role in this pathway. | ||||||
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 which, by inhibiting the degradation of polyubiquitinated proteins, can cause a build-up of substrates and potentially inhibit the function of E3 ubiquitin ligases like KLHL32 by feedback inhibition due to substrate accumulation. | ||||||
Lactacystin | 133343-34-7 | sc-3575 sc-3575A | 200 µg 1 mg | $165.00 $575.00 | 60 | |
Lactacystin is another proteasome inhibitor that irreversibly binds to the proteasome's active site. This inhibition can lead to an indirect reduction in KLHL32 activity by preventing the turnover of its ubiquitinated substrates. | ||||||
Bortezomib | 179324-69-7 | sc-217785 sc-217785A | 2.5 mg 25 mg | $132.00 $1064.00 | 115 | |
Bortezomib specifically inhibits the 26S proteasome. This inhibition can cause a backlog of proteins destined for degradation, potentially leading to the functional inhibition of E3 ubiquitin ligases including KLHL32. | ||||||