Acyltransferase Inhibitor

Sandoz 58-035 is a selective acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor. Sandoz 58-035 inhibits this enzyme in intact cells and isolated microsomal fractions. Sandoz 58-035 blocks the esterification of exogenous vesicle-derived cholesterol and the incorporation of oleic acid into cellular cholesterol esters, reducing the formation and accumulation of cholesterol esters. Sandoz 58-035 causes a slight increase in cellular free cholesterol, and at high concentrations, it also causes a slight reduction in overall cellular protein synthesis. Sandoz 58-035 can be used in studies related to cellular cholesterol regulation.

Cyano-myracrylamide is an inhibitor of zinc finger DHHC domain-containing palmitoyltransferase 20 (zDHHC20) with an IC₅₀ value of 1.35 µM. Cyano-myracrylamide also inhibits the S-Acylation of EGFR and CD36. Cyano-myracrylamide also inhibits S-acylation of Legionella E3 ligase GobX, MyD88, and Ras, which are substrates of zDHHC20, zDHHC9, and zDHHC6, respectively, in HEK293T cells expressing recombinant Legionella GobX, recombinant human MyD88, or endogenous Ras.

Pyripyropene A is an orally active, potent and selective sterol O-acyltransferase 2 (SOAT2)/acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) inhibitor, with an IC₅₀ of 0.07 µM. Pyripyropene A attenuates hypercholesterolemia and atherosclerosis in vivo.

P053 is a potent, non-competitive and selective ceramide synthase 1 (CerS1) inhibitor wirh an IC₅₀ of 0.5 μM. P053 acts as an endogenous inhibitor of mitochondrial fatty acid oxidation in muscle. Whole-body adiposity regulator.

Oxfenicine (L-p-Hydroxyphenylglycine) is an orally active carnitine palmitoyltransferase-1 inhibitor. Oxfenicine inhibits the oxidation of fatty acids in the heart, protecting cardiac tissue from necrotic damage during ischemia, and also has an inhibitory effect on cardiac tissue apoptosis. In addition, Oxfenicine promotes lipolysis in a high-fat diet rat model. Oxfenicine can be used in the study of cardiovascular and metabolic diseases.

PD 128042 (CI 976) is a potent, orally active, and selective inhibitor of ACAT (acyl coenzyme A:cholesterol acyltransferase) with an IC₅₀s of 73 nM. PD 128042 is also a potent LPAT (lysophospholipid acyltransferase) inhibitor. PD 128042 inhibits Golgi-associated LPAT activity (IC₅₀=15 μM). PD 128042 inhibits multiple membrane trafficking steps, including ones found in the endocytic and secretory pathway.

Zamaporvint (RXC004) is an orally active and selective inhibitor of Wnt. Zamaporvint targete membrane-bound o-acyltransferase Porcupine and inhibited Wnt ligand palmitoylation, secretion, and pathway activation. Zamaporvint displays a favorable pharmacokinetic profile and shows potent antiproliferative effects in Wnt ligand-dependent colorectal and pancreatic cell lines. Zamaporvint possesses multiple antitumor mechanisms and can be used in cancer research.

ST045849 (OGT-IN-2) is a small-molecule OGT inhibitor with an IC₅₀ of 30 μM against sOGT and 53 μM against ncOGT. ST045849 is applicable to research on metabolism-related diseases.

AZD7687 is a potent, selective, reversible and orally active diacylglycerol acyltransferase 1 (DGAT1) inhibitor with an IC₅₀ of 80 nM for human DGAT1. AZD7687 can be used for type 2 diabetes mellitus and obesity research.

PF-07202954 is an orally active, highly selective DGAT2 inhibitor with an IC₅₀ of 10 nM against human DGAT2 and an IC₅₀ of 17 nM against rat DGAT2. PF-07202954 reduces triglyceride synthesis, decreases hepatic triglyceride content and plasma triglyceride levels, inhibits de novo lipogenesis, and suppresses the hepatic SREBP signaling pathway as well as the expression of SREBP target genes. PF-07202954 is applicable to research related to non-alcoholic steatohepatitis.

γ-Sanshool can be isolated from Zanthoxylum piperitum. γ-Sanshool inhibits human ACAT-1 and ACAT-2 activities with IC₅₀s of 12.0 and 82.6 μM.

GPAT-IN-1 is a glycerol-3-phosphate acyltransferase (GPAT) inhibitor with an IC₅₀ value of 8.9 μM. GPAT-IN-1 can be used for the research of obesity.

DGAT1-IN-1 is a diacylglycerol O-acyltransferase 1 (DGAT1) inhibitor with a human IC₅₀ of <10 nM and a mouse IC₅₀ of <50 nM. DGAT1-IN-1 is applicable to the research of obesity-related diseases, type 2 diabetes and diabetes-related diseases.

JNJ-DGAT2-A is a selective diacylglycerol acyltransferase 2 (DGAT2) inhibitor with an IC₅₀ value of 0.14 μM in human DGAT2-expressing Sf9 insect cell membranes. JNJ-DGAT2-A can be used for the research of triglyceride (TG) synthesis.

TP-020 (MGAT2-IN-1), a chemical probe, is an orally active inhibitor of monoacylglycerol acyltransferase (MGAT2) with IC₅₀ of 7.8 and 2.4 nM for human and mouse MGAT2, respectively.

Cornuside is an iridoid glycoside with anti-allergic, anti-inflammatory, and neuroprotective activities. Cornuside exerts anti-allergic activity by downregulating the p38 MAPK, JNK, and NF-κB signaling pathways, and inhibits IgE-mediated histamine release from mast cells. Cornuside improves cognitive impairment in mice by inhibiting BACE1 activity (IC₅₀ = 55.84 μg/mL) and enhancing ChAT activity. Cornuside inhibits LPS (HY-D1056)-induced inflammatory mediators, including iNOS, COX-2, PGE2, TNF-α, IL-6, and IL-1β, by suppressing NF-κB activation.

Glabrol (Compound 1), One isoprenyl flavonoid was isolated from ethanol extract of licorice roots, is a potent and non-competitive Acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitor with an IC₅₀ value of 24.6 μM for rat liver microsomal ACAT activity.

AZD3988 is an orally active diacylglycerol acyl transferase-1 (DGAT-1) inhibitor. AZD3988 has excellent DGAT-1 (human) potency with an IC₅₀ value of 0. 6 nM. AZD3988 can be used for the research of metabolic diseases such as diabetes, obesity.

RHC 80267 (U-57908) is a potent and selective inhibitor of diacylglycerol lipase (DAGL) (with IC₅₀ of 4 μM in canine platelets). RHC-80267 inhibits cholinesterase activity with an IC₅₀ of 4 μM, thereby enhancing the relaxation evoked by acetylcholine. RHC 80267 also inhibits COX and the hydrolysis of phosphatidylcholine (PC).

BMS-963272 is an orally active and selective MGAT2 inhibitor (IC₅₀ = 7.1 nM), used for the study of metabolic disorders and inflammatory diseases.