ACAT-IN-3, a potent inhibitor of acyl-Coenzyme A: cholesterol acyltransferase (ACAT), effectively suppresses NF-κB dependent transcription.

Beauveriolide I is a cyclodepsipeptide that has been found inBeauveriaand an inhibitor of lipid droplet formation.1It inhibits lipid droplet formation when used at concentrations of 3 and 10 μM, as well as inhibits cholesterol synthesis (IC50= 0.78 μM), in primary mouse peritoneal macrophages.1,2Beauveriolide I also inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in mouse macrophage membranes (IC50= 6 μM).2 1.Namatame, I., Tomoda, H., Si, S., et al.Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979J. Antibiot. (Tokyo)52(1)1-6(1999) 2.Namatame, I., Tomoda, H., Ishibashi, S., et al.Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophagesProc. Nat. Acad. Sci. USA101(3)737-742(2004)

Beauveriolide III is a cyclodepsipeptide that has been found inBeauveriaand an inhibitor of lipid droplet formation.1It inhibits lipid droplet formation when used at concentrations of 3 and 10 μM, as well as inhibits cholesterol synthesis (IC50= 0.41 μM), in primary mouse peritoneal macrophages.1,2Beauveriolide III also inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in mouse macrophage membranes (IC50= 5.5 μM).2Beauveriolide III (25 and 50 mg/kg) reduces the size of aortic atherosclerotic lesions inLdlr-/-andApoE-/-mouse models of atherosclerosis. 1.Namatame, I., Tomoda, H., Si, S., et al.Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979J. Antibiot. (Tokyo)52(1)1-6(1999) 2.Namatame, I., Tomoda, H., Ishibashi, S., et al.Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid droplet accumulation in macrophagesProc. Nat. Acad. Sci. USA101(3)737-742(2004)

Beauvericin, a Fusarium mycotoxin, inhibits acyl-CoA:cholesterol acyltransferase (ACAT) in rat liver microsomal enzyme assays with an IC50 value of 3 μM.

Terpendole I is a fungal metabolite that has been found in A. yamanashiensis.1 It is a weak inhibitor of acyl-coenzyme A:cholesterol acyltransferase (ACAT; IC50 = 145 μM) and is active against the bacteria B. cereus and B. subtilis (MICs = 100 μg/ml for both) but not S. aureus, P. aeruginosa, or K. pneumoniae (MICs = >200 μg/ml for all) or the fungus C. albicans (MIC = 200 μg/ml).1,2 It is cytotoxic to HeLa cells with an IC50 value of 52.6 μM.3 |1. Tomoda, H., Tabata, N., Yang, D.-J., et al. Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. III. Production, isolation and structure elucidation of new components. J. Antibiot. (Tokyo) 48(8), 793-804 (1995).|2. Zhao, J.-C., Wang, Y.-L., Zhang, T.-Y., et al. Indole diterpenoids from the endophytic fungus Drechmeria sp. as natural antimicrobial agents. Phytochemistry 148, 21-28 (2018).|3. Nagumo, Y., Motoyama, T., Hayashi, T., et al. Structure-activity relationships of terpendole E and its natural derivatives. ChemistrySelect 2(4), 1533-1536 (2017).

Phenylpyropene A is a fungal metabolite originally isolated from P. griseofulvum that has enzyme inhibitory and insecticidal activities.1,2,3 It inhibits acyl-coenzyme A:cholesterol acyltransferase (ACAT; IC50 = 0.8 μM).1 Phenylpyropene A inhibits diacylglycerol acyltransferase (DGAT) in rat liver microsomes (IC50 = 78.7 μM). It induces mortality in 100% of M. persicae when used at a concentration of 5 ppm.3 |1. Kwon, O.E., Rho, M.C., Song, H.Y., et al. Phenylpyropene A and B, new inhibitors of acyl-CoA: Cholesterol acyltransferase produced by Penicillium griseofulvum F1959. J. Antibiot. (Tokyo) 55(11), 1004-1008 (2002).|2. Lee, S.W., Rho, M.C., Choi, J.H., et al. Inhibition of diacylglycerol acyltransferase by phenylpyropenes produced by Penicillium griseofulvum F1959. J. Microbiol. Biotechnol. 18(11), 1785-1788 (2008).|3. Horikoshi, R., Goto, K., Mitomi, M., et al. Identification of pyripyropene A as a promising insecticidal compound in a microbial metabolite screening. J. Antibiot. (Tokyo) 70(3), 272-276 (2017).

Acyl-Coenzyme A: cholesterol acyltransferase-1 and -2 (ACAT-1 and ACAT-2) catalyze the formation of cholesterol esters from cholesterol and long chain fatty acyl-coenzyme A, and may play a role in the development of atherosclerosis. CAY10486 inhibits human ACAT-1 and ACAT-2 equally with an IC50 value of approximately 60 μM. It also inhibits copper-mediated oxidation of low density lipoproteins by about 28% at a concentration of 3 μM.