Mevastatin (Compactin) belonging to the statin class is a hypolipidemic agent. It was isolated from the ascomycetous fungus, Penicillium citrinum by A. Endo in the 1970s, and he discovered that it acted as 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitor. Mevastatin is considered the first statin drug. The clinical trials on mevastatin were carried out in the late 1970s in Japan. The first commercial statin drug was lovastatin, the second statin, which was found in Aspergillus terreus by Merc and Endo, independently in 1979. Since lovastatin was commercialized, 10 statins were synthesized among which paravastatin was launched to the market by Sankyo in 1989. Pravastatin is used in the lowering of cholesterol and preventing cardiovascular disease. At present, statins are the largest-selling class of drugs currently taken by patients throughout the world. Sales for this one class of drugs on 2005 were $25 billion. Today an estimated 40 million people worldwide are taking statin drugs.
WHO.The top 10 leading causes of death in the world, 2000 and 2012.
2.
EndoA., KurodaM., TsujitaY. (1976) ML-236A, ML-236B, and ML-236C, new Inhibitors of cholesterogenesis produced by Penicillium citrinum. The Journal of Antibiotics, 29, 1346–1348.
3.
EndoA., KurodaM., TanzawaK. (1976) Competitive inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase by ML-236A and ML-236B fungal metabolites, having hypocholesterolemic activity. Federation of European Biochemical Societies Letters, 72, 323–326.
4.
EndoA., TsujitaT., KurodaM., TanzawaK. (1977) Inhibition of cholesterol synthesis in vitro and in vivo by ML-236A and ML-236B, competitive inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. European Journal of Biochemistry, 77, 31–36.
5.
KanekoI., Hazama-ShimadaY., EndoA. (1978) Inhibitory effects on lipid metabolism in cultured cells of ML-236B, a potent inhibitor of 3-hydroxy-3-methylglutaryl- coenzyme-A reductase. European Journal of Biochemistry, 87, 313–321.
6.
EndoA., TsujitaY., KurodaM., TanzawaK. (1979) Effects of ML-236B on cholesterol metabolism in mice and rats: lack of hypocholesterolemic activity in normal animals. Biochimica et Biophysica Acta, 575, 266–276.
7.
KurodaM., TanzawaK., TsujitaY., EndoA. (1977) Mechanism for elevation of hepatic cholesterol synthesis and serum cholesterol levels in Trition WR-1339-induced hyperlipemia. Biochimica et Biophysica Acta, 489, 119–125.
8.
TsujitaY., KurodaM., TanzawaK., KitanoN., EndoA. (1979) Hypolipidemic effects in dogs of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Atherosclerosis, 32, 307–313.
9.
KurodaM., TsujitaY., TanzawaK., EndoA. (1979) Hypolipidemic effects in monkeys of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Lipids, 14, 85–589.
10.
YamamotoA., SudoH., EndoA. (1980) Therapeutic effects of ML-236B in primary hypercholesterolemia. Atherosclerosis, 35, 259–266.
11.
MabuchiH., HabaT., TatamiR., MiyamotoS., SakaiY., WakasugiT., WatanabeA., KoizumiT., TakedaR. (1981) Effects of an Inhibitor of 3-hydroxy-3-methylglutaryl coenzyme a reductase on serum lipoproteins and ubiquinone-10 levels in patients with familial hypercholesterolemia. The New England Journal of Medicine, 305, 478–482.
12.
MabuchiH., SakaiT., SakaiY., YoshimuraA., WatanabeA., WakasugiT., KoizumiJ., TakedaR. (1983) Reduction of serum cholesterol in heterozygous patients with familial hypercholesterolemia–Additive effects of compactin and cholestyramine. The New England Journal of Medicine, 308, 609–613.
13.
Outline of CS-500 (ML-236B). Conference on the clinical trials phase II of CS-500 (ML-236B). Sankyo Co., Tokyo. August 22, 1979 and testimonies of researchers and physicians involved in the development of compactin.
14.
Mevalotin Interview Form (11th revised edition) (in Japanese). No.872189. Sankyo Company, Tokyo. October, 2015. p. 42.
15.
EndoA., MonacolinK. (1979) A new hypocholesterolemic agent produced by a Monasus species. The Journal of Antibiotics, 32, 852–854.
16.
EndoA., MonacolinK. (1980) A new hypocholesterolmic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. The Journal of Antibiotics, 33, 334–336.
17.
AlbertsA.W., HoffmanC., RothrochJ., LopezM., JoshuaH., HarrisE., PatcheH., MonaghanR., CurrieS., StapleyE., Albers-SchonbergG., HensensO., HirshfieldJ., HooqsteenK., LieschJ., SpringerJ. (1980) Mevinolin: a highly potent competitive inhibitor of hydroxymethyl-glutaryl-coenzyme A reductase and a cholesterol- lowering agent. Proceedings of National Academy of Sciences of the United States of America, 77, 3957–3961.
18.
VagelosP.R. (1991) Are prescription drug prices high?Science, 252, 1080–1084.
19.
EndoA. (2010) A historical perspective on the discovery of statins. Proceeding of the Japan Academy Sciences, Series B, 86, 488–493.
20.
BaigentC., KeechA., KearheyP.M., BlackwellL., BuckG., PollicinoC., KirbyA., SaerjinaT., PetoR., CollinsR., SimesR., ChenJ., KuronG., HuntV., HuffJ. (2005) Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90056 participants in 14 randomised trials of statins. Lancet, 366, 1267–1278.
21.
Award presentation by Joseph Goldstein. The 2008 Lasker-DeBakey Clinical Medical Research Award. Statins for lowering LDL and decreasing heart attacks by Akira Endo.
22.
GrayN.A special report on the world's top 50 pharma companies. Article-354138 pdf-Adobe Reader. May 2005.
23.
The 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (2014) Journal of American College of Cardiology, 63, 2889–2934.
