ACSM4 Inhibitors
ACSM4 inhibitors are a class of chemical compounds that specifically target and inhibit the activity of the ACSM4 enzyme, a member of the acyl-CoA synthetase medium-chain family. ACSM4 plays a crucial role in fatty acid metabolism, catalyzing the conversion of medium-chain fatty acids into their corresponding acyl-CoA derivatives, a critical step in lipid processing and energy production. These inhibitors are designed to bind to the active site of ACSM4, blocking its ability to catalyze the formation of acyl-CoA from fatty acids and CoA. By mimicking the enzyme's natural substrates or transition states, ACSM4 inhibitors can effectively compete for binding at the active site. These inhibitors often contain structural features like hydrophobic tails that resemble fatty acid chains, along with functional groups that interact with the enzyme's catalytic residues through hydrogen bonding or hydrophobic interactions.
The development of ACSM4 inhibitors is based on a deep understanding of the enzyme's three-dimensional structure, often determined through techniques like X-ray crystallography or cryo-electron microscopy. These structural insights reveal the configuration of the active site, where fatty acid substrates bind, and help identify key residues involved in the catalytic process. With this information, researchers can design inhibitors that specifically target the active site with high affinity and selectivity. In addition, computational modeling and molecular docking simulations are used to predict how well potential inhibitors will bind to ACSM4 and to optimize their chemical properties. Some ACSM4 inhibitors may also act allosterically by binding to non-catalytic sites on the enzyme, inducing conformational changes that disrupt its overall activity. These inhibitors are valuable tools for studying the role of ACSM4 in fatty acid metabolism and gaining a better understanding of how medium-chain fatty acids are processed in cells. By selectively inhibiting ACSM4, researchers can investigate its specific contributions to metabolic pathways and its interactions with other enzymes in lipid metabolism.
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| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
rac Perhexiline Maleate | 6724-53-4 | sc-460183 | 10 mg | $188.00 | ||
Perhexiline inhibits carnitine palmitoyltransferase (CPT) 1 and 2, which are key enzymes in fatty acid oxidation. ACSM4 is involved in the metabolism of short to medium chain fatty acids. By inhibiting CPT1 and CPT2, perhexiline reduces the intracellular transport of long-chain fatty acids, thus shifting cellular metabolism away from fatty acid oxidation and towards glycolysis, which can reduce the substrate availability and hence the functional activity of ACSM4. | ||||||
(+)-Etomoxir sodium salt | 828934-41-4 | sc-215009 sc-215009A | 5 mg 25 mg | $151.00 $506.00 | 3 | |
Etomoxir irreversibly inhibits CPT1, blocking the transport of fatty acids into the mitochondria, where ACSM4-related metabolism occurs. This inhibition leads to a decrease in fatty acid oxidation, diminishing the activity of ACSM4 by reducing its participation in medium-chain fatty acid metabolism. | ||||||
4-Hydroxy-L-phenylglycine | 32462-30-9 | sc-254680A sc-254680 | 5 g 10 g | $82.00 $109.00 | ||
Oxfenicine inhibits CPT1, thereby reducing the uptake of fatty acids into mitochondria for β-oxidation. This diminished fatty acid β-oxidation results in decreased substrate availability for ACSM4, thereby indirectly leading to reduced activity of ACSM4 as the demand for its metabolic function is lessened. | ||||||
1-(2,3,4-Trimethoxybenzyl)piperazine | 5011-34-7 | sc-297236 | 500 mg | $374.00 | ||
Trimetazidine partially inhibits fatty acid oxidation by blocking long-chain 3-ketoacyl CoA thiolase, which is involved in the final step of β-oxidation. This reduction in fatty acid oxidation can lead to an increased glycolytic flux, decreasing the need for ACSM4's role in medium-chain fatty acid metabolism and thus indirectly inhibiting its function. | ||||||
Ranolazine | 95635-55-5 | sc-212769 | 1 g | $109.00 | 3 | |
Ranolazine inhibits β-oxidation of fatty acids by partially inhibiting fatty acid oxidation enzymes. This leads to a shift in the energy substrate preference from fatty acids to glucose, which in turn reduces the functional demand on ACSM4 for fatty acid metabolism. | ||||||
Metformin | 657-24-9 | sc-507370 | 10 mg | $79.00 | 2 | |
Metformin activates AMP-activated protein kinase (AMPK), which inhibits acetyl-CoA carboxylase, reducing the production of malonyl-CoA. The decrease in malonyl-CoA relieves inhibition of CPT1, potentially increasing fatty acid oxidation. However, metformin also shifts cellular energy metabolism towards glucose utilization, which can decrease the functional requirement for ACSM4 activity in fatty acid metabolism. | ||||||
Nicotinic Acid | 59-67-6 | sc-205768 sc-205768A | 250 g 500 g | $62.00 $124.00 | 1 | |
Nicotinic acid inhibits lipolysis in adipose tissue, which reduces the release of free fatty acids into circulation. Lower circulating free fatty acids can lead to a reduced substrate supply for fatty acid oxidation pathways, including those involving ACSM4, thereby indirectly decreasing ACSM4 activity. | ||||||
Fenofibrate | 49562-28-9 | sc-204751 | 5 g | $41.00 | 9 | |
Fenofibrate activates peroxisome proliferator-activated receptor alpha (PPARα), which upregulates the expression of genes involved in fatty acid oxidation. Although this could initially seem to increase fatty acid oxidation, the resultant high rates of oxidation can deplete the substrates for ACSM4, leading to a paradoxical reduction in ACSM4 functional activity due to substrate scarcity. | ||||||
L-Carnitine | 541-15-1 | sc-205727 sc-205727A sc-205727B sc-205727C | 1 g 5 g 100 g 250 g | $23.00 $34.00 $79.00 $179.00 | 3 | |
L-Carnitine is essential for the transport of long-chain fatty acids into mitochondria. However, an excess of L-carnitine can lead to an increase in fatty acid oxidation rates that surpass the metabolic capacity of ACSM4, effectively reducing the relative contribution and activity of ACSM4 in the overall fatty acid metabolism process. | ||||||