Reliable quality 75330-75-5 in China Manufacturer Lovastatin powder

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Reliable quality 75330-75-5 in China Manufacturer Lovastatin powder

Lovastatin is an HMG-CoA reductase inhibitor that was initially isolated from A. terreus. It is a prodrug of its more potent metabolite, lovastatin hydroxy acid (Item No. 10010339). Both competitively inhibit HMG-CoA reductase with K_i values of 1.4 and 0.6 nM for lovastatin and the open ring, hydroxy acid form, respectively. Lovastatin (8 mg/kg/day) reduces plasma cholesterol in dogs by 29% over a three week period. It also suppresses TNF-induced NF-κB activation (IC₅₀ ~ 15 µM), which potentiates apoptosis in human myeloid leukemia cells and thus, may be useful in treating cancer. Formulations containing lovastatin were the first HMG-CoA reductase inhibitors to be used in the treatment of hypercholesterolemia.

There are two main sources of plasma cholesterol; one is exogenous cholesterol absorbed from dietary; the other is form endogenous biosynthesis in vivo, wherein the endogenous cholesterol accounts for 2/3 of the total cholesterol which makes it the primary target of lipid-lowering therapy.

Cholesterol biosynthetic pathway in vivo starts from acetyl coenzyme. HMG-CoA is first generated by the HMG-CoA synthase, and then reduced into mevalonate by HMG-CoA reductase; then went through phosphorylation to generates farnesyl pyrophosphate; further reduced to turtle-ene which finally converts to cholesterol through 20 steps including lanosterol and chain sterols, wherein the conversion of HMG-CoA to mevalonate via HMG-CoA reductase is the rate-limiting step in cholesterol synthesis, making HMG-CoA reductase is the rate-limiting enzyme. Therefore, the inhibition of HMG-CoA reductase activity can reduce the formation of endogenous cholesterol. A part of lovastatin structure, 3,5-dihydroxy heptanoic acid is quite similar with HMG-CoA and its inhibitory effect is 10,000 times higher than HMG-CoA intermediate so that it can competitively bind with HMG-CoA reductase to inhibit the synthesis of mevalonate lactone, and thus effectively reducing the speed of cholesterol synthesis in liver cells and ultimately inhibiting the biosynthesis of endogenous cholesterol.