Acyltransferase Inhibitor

Enniatin B1 is a Fusarium mycotoxin. Enniatin B1 inhibits acyl-CoA: cholesterol acyltransferase (ACAT) activity with an IC₅₀ of 73 μM in an enzyme assay using rat liver microsomes. Enniatin B1 crosss the blood-brain barrier. Enniatin B1 decreases the activation of ERK (p44/p42). Enniatin B1 inhibits moderately TNF-α-induced NF-κB activation.

Pactimibe (CS-505 free base) is a dual ACAT1/2 inhibitor with IC₅₀s of 4.9 μM and 3.0 μM, respectively. Pactimibe (CS-505 free base) inhibits ACAT with IC₅₀s of 2.0 μM, 2.7 μM, 4.7 μM in the liver, macrophages and THP-1 cells, respectively. Pactimibe (CS-505 free base) noncompetitively inhibits oleoyl-CoA with a K_i value of 5.6 μM. Moreover, Pactimibe (CS-505 free base) obviously inhibits cholesteryl ester formation with an IC₅₀ of 6.7 μM. Pactimibe (CS-505 free base) possesses anti-atherosclerotic potential with lowering plasma cholesterol activity.

DGAT-1 inhibitor 2 is an orally active DGAT-1 inhibitor with IC₅₀ values of 15 nM and 9 nM for human DGAT-1 and rat DGAT-1, respectively. DGAT-1 inhibitor 2 increases ROS concentration, GRP78, and PERK protein abundance. DGAT-1 inhibitor 2 increases SREBF1, CPT1A, and MTTP mRNA in fatty acid-treated cells. DGAT-1 inhibitor 2 improves obesity.

SD-066-4 is an orally active acyltransferase inhibitor. SD-066-4 can be used in cancer research.

ABT-046 is a potent, selective, and orally active acyl CoA:diacylglycerol acyltransferase 1 (DGAT-1) inhibitor with IC₅₀s of both 8 nM against human and mouse DGAT-1.

OSMI-2 (Compound 1b) is a cell-permeable O-linked N-acetylglucosamine transferase (OGT) inhibitor. Cells contain a large nuclear pool of partially spliced OGT transcript, and OSMI-2 increases detained intron splicing in cells.

ALT-007 is an orally active serine palmitoyltransferase (SPT) inhibitor that selectively reduces the levels of toxic very-long-chain deoxysphingolipids to enhance protein homeostasis. ALT-007 restores aging-related loss of muscle mass in a mouse model of sarcopenia. ALT-007 enhances protein homeostasis in both mouse and C. elegans models of aging and disease. ALT-007 can be used for age-related neuromuscular diseases research.

Fumonisin B2 is a selective ceramide synthase inhibitor and carcinogenic mycotoxin with toxicity comparable to that of Fumonisin B1 (HY-N6719). Fumonisin B2 inhibits de novo sphingolipid biosynthesis by blocking the amide bond formation between fatty acids and dihydrosphingosine, which leads to a massive intracellular accumulation of free dihydrosphingosine, altered sphingosine levels, subsequent inhibition of cell proliferation, and induction of cell death. Fumonisin B2 is used to investigate the pathogenesis of diseases associated with Fusarium verticillioides contamination, including equine leukoencephalomalacia, porcine pulmonary edema syndrome, human esophageal cancer, and rat hepatocellular carcinoma.

CP-113818 is a potent cholesterol acyltransferase (ACAT) inhibitor. CP-113818 can be used for the research of Alzheimer's disease.

Nevanimibe (PD-132301) is an orally active and selective acyl-coenzyme A:cholesterol O-acyltransferase 1 (ACAT1) inhibitor with an EC₅₀ of 9 nM. Nevanimibe inhibits ACAT2 with an EC₅₀ of 368 nM. Nevanimibe induces cell apoptosis and has the potential for adrenocortical cancer.

4-Hydroxyphenylglyoxylate (4-Hydroxyphenylglyoxylic acid) is an inhibitor of carnitine palmitoyltransferase I (CPT I). 4-Hydroxyphenylglyoxylate can be used to study sensitivity changes in CPT I of liver mitochondria and fatty acid oxidation by isolated hepatocytes. 4-Hydroxyphenylglyoxylate can inhibits fatty acid oxidation.

2-Fluoropalmitic acid, an acyl-CoA synthetase inhibitor, acts as a candidate anti-glioma agent. 2-Fluoropalmitic acid suppresses the viability and stem-like phenotype of glioma stem cells (GSCs). 2-Fluoropalmitic acid also inhibits proliferation and invasion of glioma cell lines.

VULM 1457 is a potent inhibitor of cholesterol acyltransferase (acyl-CoA). VULM1457 significantly reduces production and secretion of adrenomedullin (AM) and down-regulates AM receptors on human hepatoblastic cells. VULM 1457 has remarkable hypolipidaemic activity and improves the overall myocardial ischaemia-reperfusion injury outcomes. VULM 1457 has the potential for the research of diabetes mellitus and hypercholesterolaemia.

GOAT-IN-1 is an inhibitor of ghrelin O-acyltransferase (GOAT), which could be useful for the prophylaxis or treatment of obesity, diabetes, hyperlipidemia, metabolic, non-alcoholic fatty liver, steatohepatitis, sarcopenia, appetite control, alcohol/narcotic dependence, Alzheimer’s disease, Parkinson’s disease, cerebrovascular dementia, cerebral apoplexy, cerebral infarction, cardic disease, some kind of tumors.

DGAT1-IN-3 is a potent, selective and orally bioavailable inhibitor of DGAT-1, with IC₅₀s of 38 nM for human DGAT-1 and 120 nM for rat DGAT-1. DGAT1-IN-3 could be used to research of obesity, dyslipidemia, and metabolic syndrome.

Pactimibe sulfate (CS-505) is a dual ACAT1/2 inhibitor with IC₅₀s of 4.9 μM and 3.0 μM, respectively. Pactimibe sulfate (CS-505) inhibits ACAT with IC₅₀s of 2.0 μM, 2.7 μM, 4.7 μM in the liver, macrophages and THP-1 cells, respectively. Pactimibe sulfate (CS-505) noncompetitively inhibits oleoyl-CoA with a K_i value of 5.6 μM. Moreover, Pactimibe sulfate (CS-505) obviously inhibits cholesteryl ester formation with an IC₅₀ of 6.7 μM. Pactimibe sulfate (CS-505) possesses anti-atherosclerotic potential with lowering plasma cholesterol activity.

AGPAT4-IN-1 (Compound CL26) is a covalent AGPAT4 inhibitor with an IC₅₀ of 795 nM. AGPAT4-IN-1 covalently binds to AGPAT4 at Cys²²⁸ and significantly inhibits acyltransferase activity, LPA-to-PA conversion and downstream mTOR/S6K pathways. AGPAT4-IN-1 sensitizes hepatocellular carcinoma (HCC) tumors to Sorafenib (HY-10201) and significantly induces apoptosis with a synergistic response. AGPAT4-IN-1 has antitumor activity and reduces tumorigenicity and stemness in HCC xenograft mouse models.

RP-64477 is a potent inhibitor of the cholesterol esterifying enzyme Acyl-coenzyme A:cholesterol O-acyltransferase (ACAT).

GERI-BP002-A is an inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT) produced by Aspergillus fumigatus F93, which can be used in cancer research.

YM-750 is a potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor (IC₅₀=0.18 μM). ACAT catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty-acyl-coenzyme A.