VARS2 Inhibitors
Chemical inhibitors of valyl-tRNA synthetase (VARS2) can disrupt the essential process of protein synthesis through various mechanisms of action. Halofuginone, a potent molecule, inhibits the aminoacylation of tRNA by targeting charging enzymes such as VARS2. By impeding this critical step, halofuginone effectively prevents VARS2 from attaching valine to its corresponding tRNA, a crucial precursor to protein synthesis. Similarly, ganciclovir, after phosphorylation by viral kinases, can be erroneously incorporated during the tRNA valylation process managed by VARS2, leading to premature termination of the protein synthesis. This incorporation acts as a roadblock in the pathway where VARS2 is pivotal. Like ganciclovir, didanosine, another nucleoside analog, after being phosphorylated, can serve as a substrate for VARS2 and its subsequent incorporation results in the termination of the growing protein chain, thereby inhibiting VARS2's role in tRNA aminoacylation.
Additionally, ribavirin can be incorporated into RNA, affecting the activity of VARS2 by inhibiting proper valine-tRNA conjugation. This alteration hampers the VARS2 function in protein synthesis. Mupirocin, albeit selectively targeting bacterial isoleucyl-tRNA synthetase, can inform our understanding of how a similar molecule might compete with valine for the active site of VARS2, thereby inhibiting its activity. Puromycin, which mimics aminoacyl-tRNAs, can prompt premature termination during translation when incorporated into the peptide chain, effectively inhibiting VARS2-mediated protein synthesis. Other compounds, such as cycloheximide, anisomycin, chloramphenicol, tetracycline, fusidic acid, and emetine, do not directly target VARS2 but impact protein synthesis in a manner that can lead to a reduced functional demand for VARS2's enzymatic activity. Cycloheximide halts peptide elongation, anisomycin interferes with peptide bond formation, and chloramphenicol and tetracycline bind to bacterial ribosomes, all leading to a reduced need for valyl-tRNA. Fusidic acid and emetine, by stalling elongation factor G and inhibiting ribosomal translocation respectively, also contribute to a decreased requirement for VARS2's tRNA valylation activity as the overall protein synthesis slows down.
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Halofuginone | 55837-20-2 | sc-507290 | 100 mg | $1740.00 | ||
Halofuginone inhibits the aminoacylation of tRNA by charging enzymes such as VARS2. By interfering with this process, halofuginone can inhibit the activity of VARS2, which is responsible for attaching the correct amino acid (valine) to its corresponding tRNA during protein synthesis. | ||||||
Ganciclovir | 82410-32-0 | sc-203963 sc-203963A | 50 mg 250 mg | $228.00 $413.00 | 1 | |
Ganciclovir becomes phosphorylated by viral kinases and subsequently can be mistakenly incorporated by VARS2 during tRNA valylation, leading to premature chain termination during viral protein synthesis. As such, it inhibits VARS2's function in protein translation in infected cells. | ||||||
Ribavirin | 36791-04-5 | sc-203238 sc-203238A sc-203238B | 10 mg 100 mg 5 g | $62.00 $108.00 $210.00 | 1 | |
Ribavirin, a nucleoside analog, can be incorporated into the RNA structures and affect the tRNA synthetase activity of VARS2. This incorporation can inhibit proper valine-tRNA conjugation, thereby inhibiting VARS2's function in protein synthesis. | ||||||
Puromycin | 53-79-2 | sc-205821 sc-205821A | 10 mg 25 mg | $163.00 $316.00 | 436 | |
Puromycin mimics the structure of aminoacyl-tRNAs and can inhibit VARS2 by causing premature chain termination during translation when incorporated into the growing peptide chain, effectively inhibiting protein synthesis. | ||||||
Cycloheximide | 66-81-9 | sc-3508B sc-3508 sc-3508A | 100 mg 1 g 5 g | $40.00 $82.00 $256.00 | 127 | |
Cycloheximide inhibits eukaryotic peptide elongation by preventing translocation steps in protein synthesis. While not directly inhibiting VARS2, the reduction in protein synthesis demand can indirectly lead to a functional inhibition of VARS2's role in tRNA aminoacylation. | ||||||
Anisomycin | 22862-76-6 | sc-3524 sc-3524A | 5 mg 50 mg | $97.00 $254.00 | 36 | |
Anisomycin interferes with peptide bond formation on the ribosome, which can indirectly inhibit VARS2 by reducing the efficiency of protein synthesis and thus the utilization of aminoacylated tRNAs produced by VARS2. | ||||||
Chloramphenicol | 56-75-7 | sc-3594 | 25 g | $53.00 | 10 | |
Chloramphenicol binds to bacterial ribosomes and inhibits protein synthesis. While it does not directly inhibit VARS2, its action can reduce the overall demand for valyl-tRNA, thus indirectly inhibiting the functional role of VARS2 in the protein synthesis pathway. | ||||||
Tetracycline | 60-54-8 | sc-205858 sc-205858A sc-205858B sc-205858C sc-205858D | 10 g 25 g 100 g 500 g 1 kg | $62.00 $92.00 $265.00 $409.00 $622.00 | 6 | |
Tetracycline binds to the 30S subunit of bacterial ribosomes, inhibiting protein synthesis. Similar to chloramphenicol, it could indirectly inhibit VARS2 by reducing the demand for aminoacylated tRNAs in protein synthesis. | ||||||
Fusidic acid | 6990-06-3 | sc-215065 | 1 g | $292.00 | ||
Fusidic acid inhibits the turnover of elongation factor G (EF-G) from the ribosome. Although it is a specific inhibitor of bacterial protein synthesis, by analogy, the reduction in protein synthesis demand can indirectly inhibit the function of VARS2. | ||||||
Emetine | 483-18-1 | sc-470668 sc-470668A sc-470668B sc-470668C | 1 mg 10 mg 50 mg 100 mg | $352.00 $566.00 $1331.00 $2453.00 | ||
Emetine inhibits eukaryotic ribosomal translocation. While not a direct inhibitor of VARS2, the subsequent decrease in protein synthesis could lead to a reduced need for valyl-tRNA, potentially causing an indirect functional inhibition of VARS2. | ||||||