ldl

LDL-IN-3 shows anti-atherosclerotic and antioxidant activities.

Lifibrol (U-83860) is an inhibitor of cholesterol synthesis.Lifibrol has anticholesterol and hypolipidemic properties and promotes the conversion of LDL Apo B-100 in patients with hypercholesterolemia and mixed hyperlipidemia.

Probucol is an anti-hyperlipidemic drug initially developed in the treatment of coronary artery disease by lowering the level of cholesterol in the bloodstream by increasing the rate of LDL catabolism.

Atorvastatin Sodium (Lipitor) is a competitive inhibitor of HMG-CoA reductase and increases the expression of low density lipoprotein (LDL) receptors on hepatocytes. Atorvastatin Sodium treatment inhibits aquaporin 4 to reduce ischaemic brain oedema.

Pep 2-8 ammonium salt is Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. Potent inhibitor of PCSK9 binding to LDL receptor (IC50 = 0.8 μM). Restores LDL uptake in HepG2 cells treated with PCSK9.

Imanixil (HOE-402 free base) is an LDL receptor (LDLR) inducer, a hypolipidemic and hypocholesterolemic compound with antiatherogenic activity that inhibits the production of very low-density lipoproteins (VLDLs).Imanixil acts by stimulating the LDL receptor pathway.

T0901317 is a potent and selective agonist for both LXR and FXR, with EC50 of ~50 nM and 5 μM, respectively; it inhibits nuclear factor/κB (NF/κB).

Isorhamnetin (3-methylquercetin) is the methylated metabolite of quercetin. Quercetin is an important dietary flavonoid with in vitro antioxidant activity. Isorhamnetin prevents endothelial cell injuries from oxidized LDL via inhibition of lectin-like ox-LDL receptor-1 upregulation, interference of ox-LDL-mediated intracellular signaling pathway (p38MAPK activation, NF-kappaB nuclear translocation, eNOS expression) and the antioxidant activity of isorhamnetin. Isorhamnetin prevents endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin II. Isorhamnetin appears to be a potent drug against esophageal cancer due to it's in vitro potential to not only inhibit proliferation but also induce apoptosis of Eca-109 cells.

Ro 48-8071 fumarate is an inhibitor of OSC(Oxidosqualene cyclase; IC50=6.5 nM) that has low-density lipoprotein (LDL) cholesterol lowering activity.

Campesterol ((24R)-5-Ergosten-3β-ol) is a plant sterol with cholesterol lowering and anticarcinogenic effects, it and other plant sterols often decrease LDL cholesterol levels overall. Campesterol has anti-inflammatory effect, it inhibits several pro-inflammatory and matrix degradation mediators typically involved in osteoarthritis- induced cartilage degradation, also sometimes used to treat some specific prostate conditions.

Polydatin (Piceid), the glycoside of Resveratrol, is originally isolated from the Chinese herb Polygonum cuspidatum. The compound can inhibit platelet aggregation and elevate the ratios of LDL-C/HDL-C and TC/HDL-C. In the myocardial cell, white blood cell, vascular smooth muscle cell, and endothelial cell, Polydatin can inhibit ICAM-1 expression, elevate Ca2+, weaken white blood cell-endothelial cell adhesion, and activate KATP channels.

COG 133 TFA is a fragment of Apolipoprotein E (APOE) peptide. COG 133 TFA competes with the ApoE holoprotein for binding the LDL receptor, with potent anti-inflammatory and neuroprotective effects. COG 133 TFA is also a nAChR antagonist with an IC 50 of 445 nM [1] [2] .

(±)9-HODE is one of the two racemic monohydroxy fatty acids resulting from the non-enzymatic oxidation of linoleic acid. Approximately equal proportions of both isomers are found in mitochondrial and plasma membranes of rabbit reticulocytes. [1][2] Oxidized LDL contains significant amounts of esterified 9- and 13-HpODEs and HODEs. [3][4]

Cleomiscosin C has antioxidant activity, it protects against the oxidative modification of apoB-100 induced by either Cu2+ or HOCl ( IC50s of 23.6 and 3.9 microM, respectively), suggests that it could be beneficial in preventing LDL oxidation in atheroscl

Ferrichrome (iron-free) is a hydroxamate siderophore produced by various fungi (including U. sphaerogena) that facilitates iron chelation and uptake by these organisms and is also used by bacteria as a heterologous siderophore , including Pseudomonas aeruginosa and Vibrio parahaemolyticus. Ferrichrome (iron-free) (0.8 μM) inhibits concanavalin A-induced proliferation of mouse splenic monocytes and reduces the number of concanavalin A-stimulated CD4+ T cells. It also inhibits heme-catalyzed oxidation of LDL by hydrogen peroxide in a concentration-dependent manner.

N-Acetyl lysyltyrosylcysteine amide acetate is an effective and selective tripeptide inhibitor of myeloperoxidase (MPO). N-Acetyl lysyltyrosylcysteine amide acetate inhibits MPO-dependent hypochlorous acid (HOCl) generation, protein nitration, and LDL ox

(±)14(15)-EET is a metabolite of arachidonic acid that is formed via epoxidation of arachidonic acid by cytochrome P450.[1],[2] It prevents increases in leukotriene B4, ICAM-1, and chemokine (C-C motif) ligand 1 (CCL2) induced by oxidized LDL in primary rat pulmonary artery endothelial cells (RPAECs) when used at a concentration of 1 μM.[3] (±)14(15)-EET induces dilation of preconstricted isolated canine coronary arterioles (EC50 = 0.2 pM).[4] It reduces myocardial infarct size as a percentage of the area at risk in a canine model of ischemia-reperfusion injury induced by left anterior descending coronary artery (LAD) occlusion when administered at a dose of 0.128 mg/kg prior to occlusion or reperfusion.[5] Reference：[1]. Chacos, N., Falck, J.R., Wixtrom, C., et al. Novel epoxides formed during the liver cytochrome P-450 oxidation of arachidonic acid. Biochem. Biophys. Res. Commun. 104(3), 916-922 (1982).[2]. Oliw, E.H., Guengerich, F.P., and Oates, J.A. Oxygenation of arachidonic acid by hepatic monooxygenases. Isolation and metabolism of four epoxide intermediates. J. Biol. Chem. 257(7), 3771-3781 (1982).[3]. Jiang, J.-X., Zhang, S.-J., Xiong, Y.-K., et al. EETs attenuate ox-LDL-induced LTB4 production and activity by inhibiting p38 MAPK phosphorylation and 5-LO/BLT1 receptor expression in rat pulmonary arterial endothelial cells. PLoS One 10(6), e0128278 (2015).[4]. Oltman, C.L., Weintraub, N.L., VanRollins, M., et al. Epoxyeicosatrienoic acids and dihydroxyeicosatrienoic acids are potent vasodilators in the canine coronary microcirculation. Circ. Res. 83(9), 932-939 (1998).[5]. Nithipatikom, K., Moore, J.M., Isbell, M.A., et al. Epoxyeicosatrienoic acids in cardioprotection: Ischemic versus reperfusion injury. Am. J. Physiol. Heart Circ. Physiol. 291(2), H537-H542 (2006).

Oxidized low-density lipoprotein (oxLDL) particles contain low molecular weight species which are cytotoxic and pro-atherogenic. Many of these substances were recently isolated and purified from oxLDL, and identified as phosphatidylcholine species containing a fragmented, oxidized short-chain fatty acid remnant at the sn-2 position. KDdiA-PC is one of the most potent CD36 ligands among the oxLDL species. KDdiA-PC confers CD-36 scavenger receptor binding affinity to LDL at a frequency of only two to three KDdiA-PC molecules/LDL particle, and may be one of the more important structural determinants of oxLDL.

(±)9-HODE cholesteryl ester was originally extracted from atherosclerotic lesions and shown to be produced by Cu2+-catalyzed oxidation of LDL. Later studies determined that 15-LO from rabbit reticulocytes and human monocytes were able to metabolize cholesteryl linoleate, a major component of LDL, to 9-HODE cholesteryl ester.

Herboxidiene is a polyketide originally isolated from S. chromofuscus that has diverse biological activities.[1],[2,][3],[4],[5] It inhibits growth of HeLa S3, SK-MEL-2, PC3, A549, and EBC-1 cells with GI50 values ranging from 7.4 to 62 nM.3 Herboxidiene is cytostatic against human umbilical vein endothelial cells (HUVECs; (IC50 = 26 nM)) and inhibits VEGF-induced invasion and tube formation of serum-starved HUVECs in a concentration-dependent manner, indicating antiangiogenic activity.[4] Herboxidiene (0.05 μM) inhibits HIF-1α mRNA splicing and reduces HIF-1α protein levels in HepG2 cells grown under hypoxic conditions. It also inhibits splicing of p27Kip mRNA in HeLa cells in a concentration-dependent manner via interaction with the SAP155 subunit of the SF3b complex.[2] Herboxidiene (0.1 and 1 μM) increases LDL receptor promoter-driven transcription in a cell-based reporter assay.[5] It also exhibits herbicidal activity against wild buckwheat, morning glory, maize, hemp sesbania, and rapeseed when applied at 0.069 kg/hectare.[1]

(±)9-HpODE is a racemic mixture of the fatty acid hydroperoxide product (9(S)-HpODE) formed from lipoxygenase action on linoleic acid. It shows antimicrobial activity against various fungal and bacterial pathogens and thus may play a role in plant defense. In mammalian species, monocyte-induced oxidization of LDL generates significant amounts of esterified 9-HpODE, which is rapidly reduced to 9-HODE.

Stachybotramide preferentially stimulate the plasma cholesteryl ester transfer protein (CETP)-mediated transfer of cholesteryl esters (CE) from high density lipoprotein (HDL) to both very low density lipoprotein (VLDL) and low density lipoprotein (LDL).

Quercetin 7-glucuronide (Quercetin 7-O-β-glucuronide), a Quercetin metabolite found in Madagascarian Uncarina species, has the capability to inhibit LDL oxidation [1].

(±)13-HODE cholesteryl ester was originally extracted from atherosclerotic lesions and shown to be produced by Cu2+-catalyzed oxidation of LDL. Later studies determined that 15-LO from rabbit reticulocytes and human monocytes were able to metabolize cholesteryl linoleate, a major component of LDL, to 13-HODE cholesteryl ester.

Tafolecimab (IBI-306), a human IgG2 monoclonal antibody, specifically targets and binds to PCSK-9, thus inhibiting PCSK-9-mediated endocytosis of the LDL receptor. This action enhances the clearance of LDL-C, resulting in a decrease in LDL-C levels. Tafolecimab has potential applications in hypercholesterolemia research [1].

GW841819X is an analogue of (+)-JQ1 and a novel inhibitor of BET bromodomains. GW841819X was a single enantiomer but of undefined chirality at the 4-position of the benzodiazepine ring3. GW841819X and JQ1 were recently discovered that bind to the acetyl-lysine binding pocket of BET bromodomains with Kd ranges from 50 to 370 nM [1]. GW841819X bounded to both the individual BD1 and BD2 domains with affinities of 46 and 52.5 nM, respectively. GW841819X-Brd3 interaction was estimated to be around 70 nM4. GW841819X displayed activity in vivo against NUT-midline carcinoma, multiple myeloma, mixed-lineage leukemia, and acute myeloid leukemia1. It also potent induced the ApoA1 reporter gene with an EC50 of 440 nM. It had very little effect on LDL-R luciferase activity at the concentrations at which it induces ApoA1 expression, suggesting that the effect is indeed specific3. GW841819X competed directly with GATA1 site for BD1 binding and also specifically blocked the interaction between Brd3 and acetylated GATA14. Recent findings reported that GW841819X are chose as an interest compound to further develop into potential drugs against diseases including cancer, HIV infection and heart disease2.

Alirocumab is a human monoclonal antibody that inhibits PCSK9. It is produced by recombinant DNA technology in Chinese hamster ovary cell suspension culture.

R-IMPP is an inhibitor of PCSK9 translation. R-IMPP stimulates uptake of LDL-C in hepatoma cells by increasing LDL-R levels, without altering levels of secreted transferrin.

6,8-Diprenyleriodictyol is an antioxidant, which inhibits Cu(2+)-mediated oxidation of human low density lipoprotein (LDL).

PCSK9-IN-11 (compound 5r) is a potent PCSK9 inhibitor with oral activity. PCSK9-IN-11 shows inhibitory activity of PCSK9 transcription in HepG2 cells (IC50= 5.7 μM). PCSK9-IN-11 can increase LDL receptor (LDLR) protein level. PCSK9-IN-11 can be used for atherosclerosis research.

PCSK9 modulator-3 (Compound 13) is a potent PCSK9 modulator with an EC 50 value of 2.46 nM that has the potential in the hyperlipidemia research. PCSK9 is a recently proved target for lowering low-density lipoprotein cholesterol (LDL-C) [1].

PCSK9-IN-13 is a potent inhibitor of PCSK9, effectively preventing the binding of PCSK9 to low-density lipoprotein (LDL) receptors through its mechanism of action. It exhibits this inhibitory activity with an IC 50 value of 537 nM.

ASM-IN-1 is a potent, orally active inhibitor of acid sphingomyelinase (ASM) with an IC50 of 1.5 µM, demonstrating antiatherosclerotic and anti-inflammatory activity. It effectively reduces lipid plaques in the aortic arch and aorta, along with decreasing plasma ceramide concentrations and oxidized LDL (Ox-LDL) levels [1].

Frovocimab (LY 3015014), a humanized IgG4 monoclonal antibody (mAb), acts by neutralizing PCSK9. This mechanism effectively prevents PCSK9 from binding to the LDL receptor (LDLR) while allowing for the normal proteolytic cleavage of intact PCSK9 [1].

Mocravimod is an agonist of sphingosine 1-phosphate receptor type 1. Mocravimod ameliorates atherosclerosis in LDL-R-/- mice. KRP-203 attenuates rat autoimmune myocarditis. KRP-203 combined with cyclosporine prolonged graft survival and abrogated transpla

Anacetrapib (MK-0859) (MK0859) is an effective, specific, reversible rhCETP and mutant CETP(C13S) inhibitor (IC50: 7.9 nM and 11.8 nM). Anacetrapib reduces the transfer of cholesteryl ester from HDL to LDL and/or VLDL thereby, producing an increase in serum HDL-cholesterol levels and a decrease in serum LDL-cholesterol levels.

Bococizumab(PF-04950615) is a humanized mAb against PCSK9 and an inhibitor of the synthesis of PCSK9 in the liver that reduces the amount of low-density lipoprotein cholesterol (LDL-C) in the blood.Bococizumab is used to treat hypercholesterolemia.

GW590735 is a potent and selective agonist of PPARα with an EC50 value of 4 nM for the expression a GAL4-responsive reporter gene and at least 500-fold selectivity versus PPARγ and PPARδ. GW590735 significantly increased HDL cholesterol, decreased LDL and VLDL cholesterol, and significantly reduced triglycerides. Maximal increases in HDL cholesterol were 37%, 53%, and 84% with fenofibrate, torcetrapib, and GW590735, respectively.

Bempedoic acid-d4 is a deuterated compound of Bempedoic acid. Bempedoic acid has a CAS number of 738606-46-7. ETC-1002, also known as ESP-55016 and Bempedoic acid, is an orally available, once-daily LDL-C lowering small molecule designed to lower elevated levels of LDL-C and to avoid side effects associated with existing LDL-C lowering therapies. Bempedoic acid is absorbed rapidly in the small intestine and enters the liver through cell surface receptors different from those transporters that selectively take up statins. Bempedoic acid is a regulator of lipid and carbohydrate metabolism.

20-HC-Me-Pyrrolidine was A potent inhibitor of Aster protein, with IC50 values of 0.11 μM, 0.06 μM and 0.71 μM for Aster A, Aster B and Aster C, respectively. 20-HC-Me-Pyrrolidine prevents Aster protein from binding and transferring cholesterol and inhibits the movement of low-density lipoprotein (LDL) cholesterol into the endoplasmic reticulum (ER).

Dim16, a dual inhibitor of PCSK9/HMG-CoAR, demonstrates potent activity with an IC50 of 19 nM against PCSK9 and significantly impedes PCSK9-LDLR interaction with an IC50 of 0.8 nM, leading to an enhanced LDL uptake in HepG2 cells [1].

Recaticimab (SHR-1209) is a humanized monoclonal antibody targeting PCSK9 to enhance the degradation of this enzyme. By binding to PCSK9, Recaticimab elevates low-density lipoprotein (LDL) receptor presence on hepatocyte surfaces, consequently lowering plasma LDL levels and aiding in blood lipid reduction. This mechanism positions Recaticimab as a promising therapeutic for hypercholesterolemia [1] [2].

Rosuvastatin Sodium is a competitive HMG-CoA reductase (HMGCR) inhibitor (IC50: 11 nM) that effectively blocks hERG currents (IC50: 195 nM). Rosuvastatin Sodium reduces the expression of mature hERG and inhibits the interaction of heat shock protein 70 (Hsp70) with hERG protein.

N-Acetyldopamine dimer-2 (compound 2), an N-acetyldopamine dimer derived from the yellow powder of Periostracum Cicadae, exhibits antioxidant and anti-inflammatory properties. It notably inhibits oxidation of oxidized low-density lipoprotein (LDL), reduces reactive oxygen species (ROS) generation and nitric oxide (NO) production, and suppresses NF-κB activity [1].

Tirzepatide (LY-3298176) is a dual agonist of glucose-dependent polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor with neuroprotective activity for the study of diabetes and obesity.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor. Potent inhibitor of PCSK9 binding to LDL receptor (IC50 = 0.8 μM). Restores LDL uptake in HepG2 cells treated with PCSK9.

Torcetrapib (CP-529414) is a cholesteryl ester transfer protein (CETP) inhibitor that reduces the heterotypic transfer of cholesteryl ester from HDL to LDL and/or VLDL. Torcetrapib failed in phase III trials due to excess deaths.

Gemcabene calcium , a first-in-class lipid-lowering agent, lowers low-density lipoprotein cholesterol (LDL-C), decreases triglycerides, and raises high-density lipoprotein cholesterol (HDL-C) andexerting anti-inflammatory activity, lowers pro-inflammatory acute-phase protein, C-reactive protein (CRP).

Cleomiscosin A is derived from Acer okamotoanum leaf and twig and shows inhibitory activity to TNF-α secretion of the mouse peritoneal macrophages. Cleomiscosin A can be used in studies about the prevention of LDL oxidation in atherosclerotic lesions.

beta-Amyrin acetate inhibits HMG-CoA Reductase (HMGCR) and sEH activity with IC50 of 3.4 μM. beta-Amyrin acetate has anti-inflammatory, antifungal, antioxidant, and anti-hyperlipidemic activities.