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Chemical Compound Review

Mevacor     [(1S,3R,7R,8S,8aS)-8-[2- [(2R,4R)-4-hydroxy...

Synonyms: mevinolin, lovastatin, Monacolin K, MK-803, MK803, ...
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Disease relevance of lovastatin

  • We developed vector plasmids for the transformation of Halobacterium halobium, using the replicon region from the halobacterial phage H or from the plasmid pHH1 together with a DNA fragment conferring resistance to mevinolin [1].
  • Mevinolin improved serum lipid levels and reduced albuminuria in 5/6 nephrectomy rats without causing significant alterations in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)[2]
  • Abolition of mevinolin-induced growth inhibition in human fibroblasts following transformation by simian virus 40 [3].
  • Proteinuria was reduced by antihypertensive therapy (P < .001) and lipid-lowering therapy (P < .05) (16-week values: 1.069 +/- 0.167 g/d in untreated rats, 0.663 +/- 0.164 g/d in the Lova group, 0.392 +/- 0.051 g/d in the AH group, and 0.176 +/- 0.035 g/d in the AH/Lova group).(ABSTRACT TRUNCATED AT 250 WORDS)[4]
  • DNA histograms suggested that mevinolin arrests neuroblastoma cells in both the G1 and G2/M compartments of the cell cycle [5].

Psychiatry related information on lovastatin


High impact information on lovastatin


Chemical compound and disease context of lovastatin


Biological context of lovastatin

  • Two therapeutic measures that seem to increase the synthesis of LDL receptors are interruption of the enterohepatic circulation of bile acids with either bile-acid sequestrants or the ileal-exclusion operation, and competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase with mevinolin or compactin [13].
  • A genetic determinant for resistance to the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor mevinolin was isolated by "shotgun cloning" into a derivative of the endogenous H. volcanii plasmid pHV2, to form pWL2, which transforms sensitive H. volcanii to mevinolin resistance at high frequency [14].
  • To determine the mechanism for the LDL-lowering effect, we administered 131I-labeled LDL intravenously to six FH heterozygotes before and during treatment with mevinolin and calculated the apparent fractional catabolic rate (FCR) and synthetic rate for LDL [15].
  • At a concentration of 1 microM mevinolin, the cardiac cells became quiescent and electrical stimulation induced action potentials of short duration without contraction [16].
  • A frequent loss of all vectors (including pWL102) was observed in Hf. volcanii, where >90% of the mevinolin-resistant colonies obtained after transformation had lost the vector, presumably because of restriction endonuclease activity and concomitant recombination of the mevinolin resistance marker with the chromosome [1].

Anatomical context of lovastatin


Associations of lovastatin with other chemical compounds

  • Normal cholesterol levels with lovastatin (mevinolin) therapy in a child with homozygous familial hypercholesterolemia following liver transplantation [22].
  • Measurements of incorporation of (3H)acetate into neuroblastoma sterols and ubiquinones 24 h after implantation of osmotic pumps showed that mevinolin produced a marked inhibition of isoprenoid synthesis in the tumors in vivo [8].
  • The hypothesis that short-term regulation of HMG-CoA reductase in tissues is quickly reflected by corresponding variations in plasma MVA was tested by using a specific inhibitor of HMG-CoA reductase, mevinolin, to block MVA synthesis [23].
  • To determine the effectiveness of this combination and the mechanisms of lowering LDL levels, we measured turnover rates of LDL apoprotein (apo-LDL) before and during treatment with mevinolin and colestipol in eight patients with heterozygous familial hypercholesterolemia [13].
  • To identify such signals, we arrested seedling development by specifically blocking the MVA pathway with mevinolin (MEV) or the MEP pathway with fosmidomycin (FSM) and searched for MEV-resistant Arabidopsis mutants that also could survive in the presence of FSM [24].
  • The replication of dl1520 in ATC cells was enhanced by lovastatin treatment, and a significant increase of the expression of the early gene E1A 13 S and the late gene Penton was observed in lovastatin-treated cells [25].
  • Lovastatin, by targeting mevalonate synthesis, is a potent inducer of the ISR through a novel and as yet unrecognized mechanism [26].

Gene context of lovastatin


Analytical, diagnostic and therapeutic context of lovastatin


  1. Transformation of Halobacterium halobium: development of vectors and investigation of gas vesicle synthesis. Blaseio, U., Pfeifer, F. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  2. Pharmacologic treatment of hyperlipidemia reduces glomerular injury in rat 5/6 nephrectomy model of chronic renal failure. Kasiske, B.L., O'Donnell, M.P., Garvis, W.J., Keane, W.F. Circ. Res. (1988) [Pubmed]
  3. Abolition of mevinolin-induced growth inhibition in human fibroblasts following transformation by simian virus 40. Larsson, O., Barrios, C., Latham, C., Ruiz, J., Zetterberg, A., Zickert, P., Wejde, J. Cancer Res. (1989) [Pubmed]
  4. Combined antihypertensive and lipid-lowering therapy in experimental glomerulonephritis. Rubin, R., Silbiger, S., Sablay, L., Neugarten, J. Hypertension (1994) [Pubmed]
  5. Differentiation of neuroblastoma cells induced by an inhibitor of mevalonate synthesis: relation of neurite outgrowth and acetylcholinesterase activity to changes in cell proliferation and blocked isoprenoid synthesis. Maltese, W.A., Sheridan, K.M. J. Cell. Physiol. (1985) [Pubmed]
  6. Effects of exercise and lovastatin on serum creatine kinase activity. Thompson, P.D., Gadaleta, P.A., Yurgalevitch, S., Cullinane, E., Herbert, P.N. Metab. Clin. Exp. (1991) [Pubmed]
  7. Platelet-mediated cholesterol accumulation in cultured aortic smooth muscle cells. Kruth, H.S. Science (1985) [Pubmed]
  8. Suppression of murine neuroblastoma growth in vivo by mevinolin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Maltese, W.A., Defendini, R., Green, R.A., Sheridan, K.M., Donley, D.K. J. Clin. Invest. (1985) [Pubmed]
  9. Regulation of plasma levels of low-density lipoprotein cholesterol: interpretation of data on low-density lipoprotein turnover in man. Meddings, J.B., Dietschy, J.M. Circulation (1986) [Pubmed]
  10. Role of mevalonate in regulation of cholesterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase in cultured cells and their cytoplasts. Popják, G., Clarke, C.F., Hadley, C., Meenan, A. J. Lipid Res. (1985) [Pubmed]
  11. The effects of mevinolin and neomycin alone and in combination on plasma lipid and lipoprotein concentrations in type II hyperlipoproteinemia. Hoeg, J.M., Maher, M.B., Bailey, K.R., Brewer, H.B. Atherosclerosis (1986) [Pubmed]
  12. Effects of monoterpenes and mevinolin on murine colon tumor CT-26 in vitro and its hepatic "metastases" in vivo. Broitman, S.A., Wilkinson, J., Cerda, S., Branch, S.K. Adv. Exp. Med. Biol. (1996) [Pubmed]
  13. Influence of combined therapy with mevinolin and interruption of bile-acid reabsorption on low density lipoproteins in heterozygous familial hypercholesterolemia. Grundy, S.M., Vega, G.L., Bilheimer, D.W. Ann. Intern. Med. (1985) [Pubmed]
  14. Shuttle vectors for the archaebacterium Halobacterium volcanii. Lam, W.L., Doolittle, W.F. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  15. Mevinolin and colestipol stimulate receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Bilheimer, D.W., Grundy, S.M., Brown, M.S., Goldstein, J.L. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  16. Mevinolin, an inhibitor of cholesterol biosynthesis, drastically depresses Ca2+ channel activity and uncouples excitation from contraction in cardiac cells in culture. Renaud, J.F., Schmid, A., Romey, G., Nano, J.L., Lazdunski, M. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  17. Isoprenylation is required for the processing of the lamin A precursor. Beck, L.A., Hosick, T.J., Sinensky, M. J. Cell Biol. (1990) [Pubmed]
  18. Hydroxymethylglutaryl-coenzyme A reductase-containing hepatocytes are distributed periportally in normal and mevinolin-treated rat livers. Singer, I.I., Kawka, D.W., Kazazis, D.M., Alberts, A.W., Chen, J.S., Huff, J.W., Ness, G.C. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  19. Modulation of human lymphocyte responses by low density lipoproteins (LDL): enhancement but not immunosuppression is mediated by LDL receptors. Cuthbert, J.A., Lipsky, P.E. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  20. The influence of mevinolin on the adrenal cortical response to corticotropin in heterozygous familial hypercholesterolemia. Illingworth, D.R., Corbin, D. Proc. Natl. Acad. Sci. U.S.A. (1985) [Pubmed]
  21. Testis-specific transcription initiation sites of rat farnesyl pyrophosphate synthetase mRNA. Teruya, J.H., Kutsunai, S.Y., Spear, D.H., Edwards, P.A., Clarke, C.F. Mol. Cell. Biol. (1990) [Pubmed]
  22. Normal cholesterol levels with lovastatin (mevinolin) therapy in a child with homozygous familial hypercholesterolemia following liver transplantation. East, C., Grundy, S.M., Bilheimer, D.W. JAMA (1986) [Pubmed]
  23. Plasma mevalonate as a measure of cholesterol synthesis in man. Parker, T.S., McNamara, D.J., Brown, C.D., Kolb, R., Ahrens, E.H., Alberts, A.W., Tobert, J., Chen, J., De Schepper, P.J. J. Clin. Invest. (1984) [Pubmed]
  24. Distinct light-mediated pathways regulate the biosynthesis and exchange of isoprenoid precursors during Arabidopsis seedling development. Rodríguez-Concepción, M., Forés, O., Martinez-García, J.F., González, V., Phillips, M.A., Ferrer, A., Boronat, A. Plant Cell (2004) [Pubmed]
  25. Lovastatin enhances the replication of the oncolytic adenovirus dl1520 and its antineoplastic activity against anaplastic thyroid carcinoma cells. Libertini, S., Iacuzzo, I., Ferraro, A., Vitale, M., Bifulco, M., Fusco, A., Portella, G. Endocrinology (2007) [Pubmed]
  26. Activation of the integrated stress response regulates lovastatin-induced apoptosis. Niknejad, N., Morley, M., Dimitroulakos, J. J. Biol. Chem. (2007) [Pubmed]
  27. Glucose-potentiated chemotaxis in human vascular smooth muscle is dependent on cross-talk between the PI3K and MAPK signaling pathways. Campbell, M., Allen, W.E., Sawyer, C., Vanhaesebroeck, B., Trimble, E.R. Circ. Res. (2004) [Pubmed]
  28. Transcriptional derepression of the murine Cyp1a-1 gene by mevinolin. Puga, A., Raychaudhuri, B., Nebert, D.W. FASEB J. (1992) [Pubmed]
  29. Regulation of rat liver 3-hydroxy-3-methylglutaryl coenzyme A synthase and the chromosomal localization of the human gene. Mehrabian, M., Callaway, K.A., Clarke, C.F., Tanaka, R.D., Greenspan, M., Lusis, A.J., Sparkes, R.S., Mohandas, T., Edmond, J., Fogelman, A.M. J. Biol. Chem. (1986) [Pubmed]
  30. Isoprenylation of a protein kinase. Requirement of farnesylation/alpha-carboxyl methylation for full enzymatic activity of rhodopsin kinase. Inglese, J., Glickman, J.F., Lorenz, W., Caron, M.G., Lefkowitz, R.J. J. Biol. Chem. (1992) [Pubmed]
  31. Relation of mevalonate synthesis to mitochondrial ubiquinone content and respiratory function in cultured neuroblastoma cells. Maltese, W.A., Aprille, J.R. J. Biol. Chem. (1985) [Pubmed]
  32. Effects of mevinolin on cell cycle progression and viability of tobacco BY-2 cells. Hemmerlin, A., Bach, T.J. Plant J. (1998) [Pubmed]
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