How do CETP inhibitors work?

How do CETP inhibitors work?

CETP inhibitors inhibit cholesterylester transfer protein (CETP), which normally transfers cholesterol from HDL cholesterol to very low density or low density lipoproteins (VLDL or LDL). Inhibition of this process results in higher HDL levels and reduces LDL levels.

Why did CETP inhibitors fail?

Exposure to variants in the genes that encode the targets of CETP inhibitors and statins was associated with discordant reductions in LDL-C and apoB — and with an attenuated reduction in cardiovascular events that was proportional to the change in apoB but significantly less than expected given the LDL-C change.

What is a CETP?

Cholesteryl ester transfer protein (CETP) facilitates exchange of triglycerides and cholesteryl ester between high-density lipoprotein (HDL) and apolipoprotein B100–containing lipoproteins.

What is cholesteryl ester transfer protein inhibitors?

Cholesteryl ester transfer protein (CETP) inhibitors, including dalcetrapib, evacetrapib, and anacetrapib, are novel agents that have been developed to increase serum high-density lipoprotein cholesterol (HDL-c) concentration.

What drug is a PCSK9 inhibitor?

There are two PCSK9 inhibitors, Repatha (Evolocumab) and Praluent (Alirocumab), and others are being developed at the moment. In clinical studies, these medicines have lowered people’s cholesterol levels by more than half. Early research shows they could prevent strokes and heart attacks too.

What is BOD and COD in ETP?

BOD means Biochemical oxygen demand. The microorganisms use organic matter as a food source through oxidation which oxygen is consumed. COD, Chemical Oxygen Demand, is a measure of the total quantity of oxygen required to oxidize all organic material into carbon dioxide and water.

What is the function of CETP?

CETP is a hydrophobic glycoprotein that is secreted mainly from the liver and that circulates in plasma, bound mainly to HDL. It promotes the redistribution of cholesteryl esters, triglycerides, and, to a lesser extent, phospholipids between plasma lipoproteins.

Can Repatha damage your liver?

Repatha has not been studied in patients with severe kidney or liver disease; however, Repatha is not expected to be harmful to the kidneys or liver. Although Repatha lowers levels of fats in the blood, which are risk factors for cardiovascular disease, it is not known if Repatha will reduce cardiovascular disease.

How does a CETP inhibitor affect HDL-C?

CETP inhibitors raise HDL-C by decreasing the transfer of cholesteryl esters to other lipoprotein particles such as LDL, thereby retaining more cholesterol in HDL.

How are CETP inhibitors used to treat atherosclerosis?

CETP Inhibitors. CETP is responsible for transferring cholesteryl esters from HDL to LDL or VLDL particles in exchange for TGs. Inhibition of CETP in an animal model reduced progression of atherosclerosis [73].

Are there any CETP inhibitors in the market?

Two potent CETP inhibitors (Anacetrapib and TA8995) are still in clinical development. Both are associated with a marked increase in HDLc levels and reduction in LDL-C level.

Are there any antisense oligonucleotides that inhibit CETP?

Antisense oligonucleotide-inhibited CETP mRNA could enhance macrophage reverse cholesterol transport, resulting in increase in fecal cholesterol excretion and decreased TG secretion in the liver of hyperlipidemic, CETP transgenic, LDL receptor knockout mice [51]. A more interesting approach might be manipulating substrate preference of CETP.