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How a small molecule promotes removal of excess cholesterol

JacksinPA

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https://www.sciencedaily.com/releases/2018/11/181127111001.htm

Scientists have determined the structure of the activated form of an enzyme that helps to return excess cholesterol to the liver, a study in eLife reports.

The research reveals how a drug-like chemical stimulates the action of the lecithin:cholesterol acyltransferase (LCAT) enzyme. It also suggests that future drugs using the same mechanism could be used to restore LCAT function in people with familial LCAT deficiency (FLD), a rare inherited disease that puts them at risk of eye problems, anemia and kidney failure.

LCAT helps high-density lipoprotein (HDL) -- known as the 'good' cholesterol -- to remove cholesterol from the blood by converting the lipid into a form that is easier to package and transport. There are more than 90 known mutations in LCAT, which can cause either a partial loss of activity (known as 'fish-eye disease') or full loss (FLD). Boosting LCAT activity could therefore be beneficial in treating people with coronary heart disease and LCAT deficiencies, but the mechanisms by which it can be activated are poorly understood.
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A drug that helps get rid of cholesterol would be a very good thing for a lot of people.

I only found one reference to a pharma company working on a LCAT stimulator. It was AMGEN, the California biotech. The program was terminated 2 years ago but it gave the partial structure of the drug as being a pyrazine.
 
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