Mevastatin

Mevastatin (Compactin; ML236B) inhibits HMGCR (HMG-CoA reductase) (Ki for acid form is 1 nM) which in turn inhibits isoprenoid biosynthesis and therefore blocks protein isoprenylation and reduces plasma cholesterol levels in humans. IC50 value: 1 nM (Ki)Target: HMGCRMevastatin induces apoptosis, arrests cancer cells in G1 phase and downregulates cdk 2, 4, and 6, cyclin D1 and E1, p21 and p27. Mevastatin suppresses TNF-induced NF-κB activation (IC50 = ~17 uM), which potentiates apoptosis

Mevastatin is a carboxylic ester that is pravastatin that is lacking the allylic hydroxy group. A hydroxymethylglutaryl-CoA reductase inhibitor (statin) isolated from Penicillium citrinum and from Penicillium brevicompactum, its clinical use as a lipid-regulating drug ceased following reports of toxicity in animals. It has a role as a fungal metabolite, an EC 3.4.24.83 (anthrax lethal factor endopeptidase) inhibitor, an antifungal agent, a Penicillium metabolite and an apoptosis inducer. It is a carboxylic ester, a statin (naturally occurring), a member of hexahydronaphthalenes, a member of 2-pyranones and a polyketide.|Mevastatin or compactin is a cholesterol-lowering agent isolated from Penicillium citinium. It was the first discovered agent belonging to the class of cholesterol-lowering medications known as statins. During a search for antibiotic compounds produced by fungi in 1971, Akira Endo at Sankyo Co. (Japan) discovered a class of compounds that appeared to lower plasma cholesterol levels. Two years later, the research group isolated a compound structurally similar to hydroxymethylglutarate (HMG) that inhibited the incorporation of acetate. The compound was proposed to bind to the reductase enzyme and was named compactin. Mevastatin is a competitive inhibitor of HMG-Coenzyme A (HMG-CoA) reductase with a binding affinity 10,000 times greater than the HMG-CoA substrate itself. Mevastatin is a pro-drug that is activated by in vivo hydrolysis of the lactone ring. It has served as one of the lead compounds for the development of the synthetic compounds used today.|Mevastatin is an HMG-CoA reductase inhibitor that was initially isolated from the mold Pythium ultimum. Mevastatin was the first statin to enter clinical trials.

Mevastatin (compactin) is a diterpene produced by several species of the genera Penicillium and Monascus, first reported in 1976. Mevastatin, the prototype of the statin class, is a potent competitive inhibitor of HMG-CoA reductase, a regulatory enzyme for cholesterol biosynthesis. Mevastatin has also been shown to induce apoptosis by inhibiting post-translational prenylation of proteins such as Ras, increasing eNOS mRNA and protein levels by blocking the geranylgeranylation of Rho, and inhibiting myoblast fusion. It induces cell cycle arrest in late G1 phase and may induce bone morphogenic protein-2 (BMP-2).

Molecular Weight:390.5
XLogP3:3.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:7
Exact Mass:390.24062418
Monoisotopic Mass:390.24062418
Topological Polar Surface Area:72.8
Heavy Atom Count:28
Complexity:637
Defined Atom Stereocenter Count:7
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes