LPAAT-δ Inhibitors
Chemical inhibitors of LPAAT-δ act by disrupting the enzyme's access to substrates essential for its acyltransferase activity. Triacsin C directly inhibits the action of long-chain acyl-CoA synthetase, leading to a significant drop in the cellular concentrations of acyl-CoA. This reduction directly impacts LPAAT-δ, as it relies on acyl-CoA substrates to convert lysophosphatidic acid into phosphatidic acid. Similarly, CI-976, while initially identified as an inhibitor of acyl-CoA:cholesterol acyltransferase, also diminishes the levels of acyl-CoA in the cell, thereby obstructing LPAAT-δ's functional capacity by substrate scarcity. Perhexiline and Etomoxir target carnitine palmitoyltransferase which is a crucial enzyme in fatty acid transport into mitochondria, and the inhibition of this enzyme results in a lower intracellular pool of acyl-CoA, thus indirectly inhibiting LPAAT-δ activity through substrate limitation.
Furthermore, Cerulenin hampers fatty acid synthase, curtailing the synthesis of fatty acids, the building blocks for acyl-CoA, which in turn limits LPAAT-δ activity due to reduced availability of its substrates. Statins such as Simvastatin, Atorvastatin, and Lovastatin, known for their HMG-CoA reductase inhibitory effects, can indirectly lower acyl-CoA concentrations, which is a critical determinant for LPAAT-δ activity, thus effectively inhibiting the enzyme. Gemfibrozil, a PPARα agonist, alter fatty acid metabolism and can result in decreased acyl-CoA levels, leading to the inhibition of LPAAT-δ activity. Lastly, Amlodipine modulates calcium channels, and because intracellular calcium levels are integral to the regulation of various lipid metabolic enzymes, this modulation can lead to reduced acyl-CoA production, thereby inhibiting LPAAT-δ through a lack of necessary substrates for its enzymatic action.
SEE ALSO...
| Product Name | CAS # | Catalog # | QUANTITY | Price | Citations | RATING |
|---|---|---|---|---|---|---|
Triacsin C Solution in DMSO | 76896-80-5 | sc-200574 sc-200574A | 100 µg 1 mg | $187.00 $843.00 | 14 | |
Triacsin C inhibits long-chain acyl-CoA synthetase, reducing the cellular levels of acyl-CoA, a substrate necessary for the acyltransferase activity of LPAAT-δ. This results in the direct inhibition of LPAAT-δ's ability to catalyze the conversion of lysophosphatidic acid to phosphatidic acid by reducing the availability of its required acyl-CoA substrates. | ||||||
CI 976 | 114289-47-3 | sc-203892B sc-203892 sc-203892A | 5 mg 10 mg 50 mg | $109.00 $189.00 $774.00 | 4 | |
CI-976, while known to inhibit acyl-CoA:cholesterol acyltransferase, can also decrease the acyl-CoA levels in cells, thereby inhibiting the acyltransferase activity of LPAAT-δ by lowering its substrate concentration. | ||||||
rac Perhexiline Maleate | 6724-53-4 | sc-460183 | 10 mg | $188.00 | ||
Perhexiline inhibits carnitine palmitoyltransferase (CPT), which is essential for the transport of fatty acids into mitochondria. By inhibiting CPT, perhexiline reduces the intracellular concentration of acyl-CoA, consequently inhibiting LPAAT-δ activity through substrate limitation. | ||||||
(+)-Etomoxir sodium salt | 828934-41-4 | sc-215009 sc-215009A | 5 mg 25 mg | $151.00 $506.00 | 3 | |
Etomoxir inhibits carnitine palmitoyltransferase I (CPT1) on the outer mitochondrial membrane, resulting in a reduced pool of acyl-CoA within cells, which is necessary for LPAAT-δ activity, thus inhibiting the enzyme's function by substrate deprivation. | ||||||
Cerulenin (synthetic) | 17397-89-6 | sc-200827 sc-200827A sc-200827B | 5 mg 10 mg 50 mg | $161.00 $312.00 $1210.00 | 9 | |
Cerulenin inhibits fatty acid synthase, leading to a decreased synthesis of fatty acids, which are precursors for acyl-CoA. The reduction in fatty acid production limits the availability of acyl-CoA for LPAAT-δ, thereby inhibiting its enzymatic activity. | ||||||
Simvastatin | 79902-63-9 | sc-200829 sc-200829A sc-200829B sc-200829C | 50 mg 250 mg 1 g 5 g | $31.00 $89.00 $135.00 $443.00 | 13 | |
Simvastatin, by inhibiting HMG-CoA reductase, disrupts cholesterol synthesis and can indirectly lead to reduced acyl-CoA levels, inhibiting LPAAT-δ by decreasing the availability of essential substrates. | ||||||
Atorvastatin | 134523-00-5 | sc-337542A sc-337542 | 50 mg 100 mg | $257.00 $505.00 | 9 | |
Atorvastatin inhibits HMG-CoA reductase, potentially leading to a reduction in acyl-CoA concentrations and inhibiting LPAAT-δ activity by the resulting substrate scarcity. | ||||||
Lovastatin | 75330-75-5 | sc-200850 sc-200850A sc-200850B | 5 mg 25 mg 100 mg | $29.00 $90.00 $339.00 | 12 | |
Lovastatin inhibits HMG-CoA reductase, which can indirectly result in lower acyl-CoA levels within the cell, thereby inhibiting LPAAT-δ through substrate limitation. | ||||||
Gemfibrozil | 25812-30-0 | sc-204764 sc-204764A | 5 g 25 g | $66.00 $267.00 | 2 | |
Gemfibrozil, a PPARα agonist, can decrease fatty acid and triglyceride levels, which may result in lower acyl-CoA levels, inhibiting LPAAT-δ activity due to a lack of necessary substrates. | ||||||
Amlodipine | 88150-42-9 | sc-200195 sc-200195A | 100 mg 1 g | $74.00 $166.00 | 2 | |
Amlodipine modulates calcium influx, which is essential for various lipid metabolic enzymes. Altered intracellular calcium levels can lead to reduced acyl-CoA production, thereby inhibiting LPAAT-δ activity through a deficit of substrates required for its enzymatic function. | ||||||