TMEM49 Inhibitors
Chemical inhibitors of TMEM49 can function through various mechanisms to disrupt the autophagic process in which TMEM49 is involved. Bafilomycin A1 acts by specifically inhibiting the vacuolar-type H+-ATPase. This inhibition prevents the acidification within autophagosomes, which is a necessary step for their fusion with lysosomes, a process critical for the maturation of autophagosomes where TMEM49 operates. Similarly, Chloroquine and its more potent derivative, Hydroxychloroquine, raise the pH in lysosomes and autophagosomes, which interferes with their function. This increase in pH disrupts the autophagic flux, thereby impairing the function of TMEM49 within this pathway. Lys05, akin to Chloroquine, also disrupts lysosomal acidification and, as such, inhibits autophagy, leading to a functional inhibition of TMEM49 by affecting the pathway and lysosomal function associated with TMEM49.
On the other hand, 3-Methyladenine (3-MA) and Wortmannin target the early stages of autophagosome formation through the inhibition of class III PI3K and phosphoinositide 3-kinases respectively. These enzymes are crucial for the induction of autophagy, and their inhibition leads to a decrease in autophagosome formation where TMEM49 is supposed to function. LY294002, which inhibits class I PI3Ks, impacts autophagy indirectly, thereby affecting the function of TMEM49 by disrupting the signaling pathways that regulate autophagy. Compounds such as Spautin-1 and SAR405 inhibit autophagy by promoting the degradation of autophagy-related proteins and selective inhibition of the PIK3C3/Vps34 complex, respectively, both leading to a functional inhibition of TMEM49. Moreover, NSC 185058 disrupts ATG4 function, necessary for the delipidation of ATG8 proteins, a process essential for autophagy and consequently for the functional role of TMEM49. Lastly, E64d inhibits the final stages of autophagy by inhibiting the degradation of autolysosomal contents, which also hinders the function of TMEM49 by preventing the completion of the autophagic process.
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Bafilomycin A1 | 88899-55-2 | sc-201550 sc-201550A sc-201550B sc-201550C | 100 µg 1 mg 5 mg 10 mg | $98.00 $255.00 $765.00 $1457.00 | 280 | |
Bafilomycin A1 is a specific inhibitor of the vacuolar-type H+-ATPase. By inhibiting this pump, it prevents acidification of the lumen of autophagosomes, which is necessary for the fusion with lysosomes. TMEM49 is involved in autophagosome formation; thus, inhibition of this process will inhibit the function of TMEM49 in autophagosome maturation. | ||||||
Chloroquine | 54-05-7 | sc-507304 | 250 mg | $69.00 | 2 | |
Chloroquine is a known autophagy inhibitor which raises the pH in lysosomes and autophagosomes, affecting their function. TMEM49 plays a role in autophagy, and its inhibition by chloroquine would lead to a functional inhibition of TMEM49 by disrupting the autophagic flux that TMEM49 is involved in. | ||||||
Autophagy Inhibitor, 3-MA | 5142-23-4 | sc-205596 sc-205596A | 50 mg 500 mg | $65.00 $261.00 | 113 | |
3-Methyladenine (3-MA) inhibits class III PI3K, which is crucial for the initiation of autophagosome formation. Since TMEM49 is involved in the autophagy process, inhibition of autophagosome formation by 3-MA would lead to a functional inhibition of TMEM49. | ||||||
Wortmannin | 19545-26-7 | sc-3505 sc-3505A sc-3505B | 1 mg 5 mg 20 mg | $67.00 $223.00 $425.00 | 97 | |
Wortmannin is a potent inhibitor of phosphoinositide 3-kinases which are involved in autophagy induction. TMEM49 plays a role in autophagy, and inhibition of the PI3K pathway by wortmannin would functionally inhibit TMEM49 by preventing the formation of autophagosomes, where TMEM49 functions. | ||||||
LY 294002 | 154447-36-6 | sc-201426 sc-201426A | 5 mg 25 mg | $123.00 $400.00 | 148 | |
LY294002 inhibits class I PI3Ks, which indirectly impacts autophagy. Since TMEM49 is part of the autophagic process, inhibiting PI3K with LY294002 would inhibit the function of TMEM49 by disrupting the signaling pathways that regulate autophagy and thus autophagosome formation where TMEM49 operates. | ||||||
Spautin-1 | 1262888-28-7 | sc-507306 | 10 mg | $168.00 | ||
Spautin-1 promotes the degradation of autophagy-related proteins by inhibiting ubiquitin-specific peptidases, USP10 and USP13, leading to blockage of autophagy. TMEM49 requires autophagy to function, thus Spautin-1 would functionally inhibit TMEM49 by impairing the autophagy process it is involved in. | ||||||
SAR405 | 1523406-39-4 | sc-507416 | 1 mg | $125.00 | ||
SAR405 is a potent and selective inhibitor of the PIK3C3/Vps34 complex which is involved in autophagy. Inhibition of Vps34 by SAR405 would lead to functional inhibition of TMEM49 as it interferes with autophagosome maturation, which requires TMEM49. | ||||||
NSC 185058 | 39122-38-8 | sc-507531 | 1 mg | $85.00 | ||
NSC 185058 disrupts ATG4 function, an enzyme required for autophagy, by preventing the delipidation of ATG8 proteins. TMEM49 is part of the autophagic machinery, and inhibition of ATG4 by NSC 185058 would inhibit the function of TMEM49 by impeding the autophagic process in which it is involved. | ||||||
Lys05 | 1391426-24-6 | sc-507532 | 5 mg | $140.00 | ||
Lys05 is a more potent derivative of chloroquine, which also disrupts lysosomal acidification, thereby inhibiting autophagy. Inhibition of autophagy by Lys05 would functionally inhibit TMEM49 by disrupting the autophagic pathway and lysosomal function that TMEM49 is associated with. | ||||||
hydroxychloroquine | 118-42-3 | sc-507426 | 5 g | $57.00 | 1 | |
Hydroxychloroquine, similar to chloroquine, inhibits autophagy by increasing lysosomal pH and disrupting autophagosome fusion. TMEM49, being involved in autophagy, would be functionally inhibited by hydroxychloroquine as it impairs the autophagic process that facilitates the function of TMEM49. | ||||||