cholesterol biosynthesis

Triparanol (NSC-65345) interferes with posttranslational modification of Hedgehog signaling molecules as well as the sterol sensing domain of its receptor PTCH1, leading to down-regulation of Hedgehog signaling. Triparanol suppresses human tumor growth and is an antilipemic agent with high ophthalmic toxicity.

Diallyl disulfide has antitumor effect, the effect can be enhanced by miR-200b and miR-22.

Lapaquistat is a cholesterol biosynthesis inhibitor and is the active metabolite of TAK-475. Lapaquistat can reduce statin-induced myotoxicity in lipid-lowering therapy.

7-Ketocholesterol is a metabolite of Cholesterol

AY 9944 is a specific cholesterol biosynthesis inhibitor that targets the 7-dehydrocholesterol Δ7-reductase (DHCR7) enzyme (IC50=13 nM). At high doses, AY 9944 also inhibits sterol Δ7-Δ8 isomerase in cultured embryos, leading to the accumulation of cholest-8-en-3β-ol[1][2][3]. Additionally, AY 9944 causes hypocholesterolemia and accumulation of 7DHC.

Dalvastatin (RG-12561) is an orally available inhibitor of HMG-CoA reductase and cholesterol-lowering synthesis.Dalvastatin competitively inhibits rat hepatic HMG-CoA reductase with an IC50 value of 3.4 nmol / l. Dalvastatin inhibits cholesterol biosynthesis in liver sections in rat experiments with an ED50 value of 0.9.

7-Dehydrocholesterol (Provitamin D3) down-regulates cholesterol biosynthesis in cultured Smith-Lemi-Opitz syndrome skin fibroblasts.

7α-Hydroxy-4-cholesten-3-one is an intermediate in bile acid synthesis from cholesterol, a PXR agonist, and a biomarker for bile acid loss and diseases related to defective bile acid biosynthesis. It is also the physiological substrate for [CYP8B1].

Monacolin J (Antibiotic MB 530A) is a cholesterol biosynthesis inhibitor.

E2012 is a γ-secretase modulator (GSM). E2012 inhibits 3β-hydroxysterol Δ24-reductase (DHCR24) at the final step in the cholesterol biosynthesis. E 2012 aims at Alzheimer's disease by reduction of amyloid β-42, and induces cataract following repeated doses in the rat.

Meglutol (3-Hydroxy-3-methylglutaric acid) is an antilipemic agent which lowers cholesterol, triglycerides, serum beta-lipoproteins and phospholipids. It acts by interfering with the enzymatic steps involved in the conversion of acetate to hydroxymethyl glutaryl coenzyme A as well as inhibiting the activity of HYDROXYMETHYLGLUTARYL COA REDUCTASES which is the rate-limiting enzyme in the biosynthesis of cholesterol.

Desmosterol (24-Dehydrocholesterol) is a cholesterol biosynthesis intermediate that inhibits macrophage inflammatory vesicle activation and prevents vascular inflammation and atherosclerosis.

ESI1 is a small molecule inhibitor of epigenetic silencing. This compound induces the formation of nuclear aggregates of the key lipid metabolism regulator SREBP1 2, thereby concentrating transcription co-activators to drive lipid cholesterol biosynthesis. Additionally, ESI1 promotes myelin regeneration in demyelination animal models and facilitates de novo myelination on regenerating CNS axons, reversing age-related cognitive decline.

DSP-0390 is an oral inhibitor of emopamil binding protein (EBP). It effectively suppresses the EBP enzyme, which is involved in a critical late-stage step of cholesterol biosynthesis. By inhibiting the synthesis of new cholesterol, DSP-0390 selectively induces cytotoxicity in rapidly proliferating GBM cells. In human GBM xenograft models, DSP-0390 has demonstrated significant antitumor activity.

28-Aminobetulin is a pentacyclic triterpenoid compound and a derivative of Betulin, which acts as an inhibitor of cholesterol biosynthesis.

1-(2,3-Dichlorphenyl)-piperazine (DCPP) is a potent DHCR7 inhibitor. DHCR7 is the last enzyme in cholesterol biosynthesis.

EBP-IN-1 (compound 11) is an inhibitor of emopamil binding protein (EBP), which is a sterol isomerase in the cholesterol biosynthesis pathway. This compound exhibits a long half-life in rodents and demonstrates favorable metabolic turnover and brain penetration properties. EBP-IN-1 promotes the formation of oligodendrocytes in human cortical organoids.

YM-53601 is a potent squalene synthase (SQS) inhibitor that inhibits adipogenic biosynthesis and lipid secretion in rodents.YM-53601 is a cholesterol-lowering agent that inhibits farnesyl diphosphate farnesyltransferase 1 (FDFT1).YM-53601 exhibits potential antiviral activity and enhances adriamycin-mediated HCC arrest and cell death in vivo. MJN228 is a lipid-based enzyme.

NCX-6560 is a novel NO-releasing derivative of atorvastatin, with those of atorvastatin. NCX-6560 inhibits cholesterol biosynthesis in rat smooth muscle cells with an IC50 of 1.9 μM.

CP-320626 is a highly efficient human liver glycogen phosphorylase (GP) inhibitor with cholesterol-lowering activity. It inhibits cholesterol biosynthesis by directly inhibiting CYP51 and can be used in type 2 diabetes research.

Zymostenol (5a-Cholest-8-en-3b-ol) is a RORγ agonist with an EC50 of 1 μM and serves as a late-stage precursor in cholesterol biosynthesis.

Geranyl pyrophosphate is an intermediate in the mevalonate pathway. It is formed from dimethylallyl pyrophosphate and isopentenyl pyrophosphate by geranyl pyrophosphate synthase. Geranyl pyrophosphate is used in the biosynthesis of farnesyl pyrophosphate , geranylgeranyl pyrophosphate , cholesterol, terpenes, and terpenoids.

3-Acetyl betulinaldehyde is a triterpene and derivative of the cholesterol biosynthesis inhibitor betulin that has been found inA. japonica.1It is an intermediate in the synthesis of 3-acetylbetulinic acid, as well as various lupine and germanicane triterpenes and saponins with anticancer activity.2 1.Tung, N.H., Kwon, H.-J., Kim, J.-H., et al.An anti-influenza component of the bark of Alnus japonicaArch. Pharm. Res.33(3)363-367(2010) 2.Thibeault, D., Gauthier, C., Legault, J., et al.Synthesis and structure-activity relationship study of cytotoxic germanicane- and lupane-type 3β-O-monodesmosidic saponins starting from betulinBioorg. Med. Chem.15(18)6144-6157(2007)

Cholesterol-5α,6α-epoxide (Epoxycholesterol) is the metabolite of cholesterol produced by oxidation. Cholesterol-5α,6α-epoxide induces triacylglycerol biosynthesis by binding to LXRβ following tamoxifen and PBPE application.