WIPI-4 Inhibitors
Chemical inhibitors of WIPI-4 act through various mechanisms to disrupt the autophagic process at different stages, affecting the function of WIPI-4, which plays a critical role in autophagosome formation. Wortmannin, 3-Methyladenine, LY294002, and SAR405 directly inhibit phosphoinositide 3-kinases (PI3Ks), which are essential for the initiation of autophagy. The inhibition of PI3Ks prevents the formation of PI3P, a phospholipid that recruits WIPI-4 to the site of autophagosome formation. Without the recruitment and localization function of WIPI-4, the initiation and nucleation of autophagosomes are impaired. Similarly, Spautin-1 disrupts autophagy by promoting the degradation of class III PI3K complexes, further preventing the activation of WIPI-4.
Secondary inhibitors such as Bafilomycin A1, Concanamycin A, Chloroquine, Hydroxychloroquine, and Lys05 affect WIPI-4 function by disrupting later stages of autophagy, particularly autophagosome maturation and fusion with lysosomes. Bafilomycin A1 and Concanamycin A inhibit the V-ATPase responsible for autophagosome acidification, a critical step for the degradation of autophagosomal contents, which is necessary for the recycling process in which WIPI-4 is involved. Chloroquine and Hydroxychloroquine inhibit the fusion between autophagosomes and lysosomes, leading to the accumulation of undigested autophagic vacuoles, which indirectly inhibits WIPI-4 by preventing the completion of the autophagic cycle. Lys05, a more potent derivative of chloroquine, also inhibits autophagosome-lysosome fusion, leading to similar outcomes as chloroquine and hydroxychloroquine. Finally, Torin 1 and MHY1485 affect WIPI-4 by dysregulating the balance of autophagy. Torin 1, an mTOR inhibitor, induces autophagy and could lead to excessive autophagosome formation, while MHY1485, an mTOR activator, disrupts the normal cycling and turnover of autophagosomes. Both of these perturbations can disrupt the functional activity of WIPI-4, which is finely tuned to the autophagic flux within the cell.
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Wortmannin | 19545-26-7 | sc-3505 sc-3505A sc-3505B | 1 mg 5 mg 20 mg | $66.00 $219.00 $417.00 | 97 | |
Wortmannin, a potent inhibitor of phosphoinositide 3-kinases (PI3Ks), can inhibit the activity of WIPI-4 by disrupting the PI3K complex, which is essential for autophagy initiation, a process in which WIPI-4 is involved. | ||||||
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 subsequently inhibits the initiation of autophagy, a cellular process that requires the functional participation of WIPI-4 for the formation of autophagosomes. | ||||||
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 is necessary for autophagy induction. By inhibiting PI3K, LY294002 can prevent the initiation of autophagy thereby inhibiting the function of WIPI-4 in autophagosome formation. | ||||||
Spautin-1 | 1262888-28-7 | sc-507306 | 10 mg | $165.00 | ||
Spautin-1 promotes the degradation of class III PI3K complexes by inhibiting ubiquitin-specific peptidase 10 (USP10) and USP13, thus impeding the autophagy process in which WIPI-4 plays a key role. | ||||||
SAR405 | 1523406-39-4 | sc-507416 | 1 mg | $125.00 | ||
SAR405 is a potent inhibitor of the Vps34 PI3K complex, which is crucial for the early stages of autophagy. Inhibition of Vps34 by SAR405 can lead to the functional inhibition of WIPI-4 by preventing autophagosome formation. | ||||||
Bafilomycin A1 | 88899-55-2 | sc-201550 sc-201550A sc-201550B sc-201550C | 100 µg 1 mg 5 mg 10 mg | $96.00 $250.00 $750.00 $1428.00 | 280 | |
Bafilomycin A1, a V-ATPase inhibitor, prevents the acidification of autophagosomes. This inhibition can indirectly inhibit WIPI-4 by disrupting autophagosome maturation, a step where WIPI-4 is functionally significant. | ||||||
Chloroquine | 54-05-7 | sc-507304 | 250 mg | $68.00 | 2 | |
Chloroquine inhibits the fusion of autophagosomes with lysosomes, a critical step in autophagy where WIPI-4 is also involved, leading to the functional inhibition of WIPI-4 by preventing autolysosome formation. | ||||||
hydroxychloroquine | 118-42-3 | sc-507426 | 5 g | $56.00 | 1 | |
Hydroxychloroquine, similar to chloroquine, inhibits the endosomal acidification process, which is necessary for the fusion of autophagosomes and lysosomes, thereby inhibiting the function of WIPI-4 in autophagy. | ||||||
Concanamycin A | 80890-47-7 | sc-202111 sc-202111A sc-202111B sc-202111C | 50 µg 200 µg 1 mg 5 mg | $65.00 $162.00 $650.00 $2550.00 | 109 | |
Concanamycin A, like Bafilomycin A1, is a V-ATPase inhibitor that disrupts autophagosome acidification. This inhibition can indirectly inhibit WIPI-4 by impeding autophagosome maturation. | ||||||
Lys05 | 1391426-24-6 | sc-507532 | 5 mg | $140.00 | ||
Lys05 is a dimeric chloroquine derivative that acts as a more potent autophagy inhibitor than chloroquine. It would inhibit WIPI-4 by blocking the autophagosome-lysosome fusion process, crucial for autophagic flux. | ||||||