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Chemical Compound Review

AGN-PC-00K3VI     [8-[2-(4-hydroxy-6-oxo-oxan- 2-yl)ethyl]-3...

Synonyms: SureCN1130742, CTK8D9616, AR-1H4236, AKOS015894860, AC1L1H3T, ...
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Disease relevance of lovastatin


Psychiatry related information on lovastatin


High impact information on lovastatin

  • Lovastatin for X-linked adrenoleukodystrophy [11].
  • Cholesterol lowering with lovastatin significantly improved endothelium-mediated responses in the coronary arteries of patients with atherosclerosis [12].
  • In a randomized, double-blind, placebo-controlled trial, we studied coronary endothelial responses in 23 patients randomly assigned to either lovastatin (40 mg twice daily; 11 patients) or placebo (12 patients) plus a lipid-lowering diet (American Heart Association Step 1 diet) [12].
  • Despite a 42 percent reduction in the serum level of low-density lipoprotein cholesterol in the lovastatin group, after six months of treatment the amount of stenosis seen in the second angiogram was 46 +/- 20 percent in the placebo group, as compared with 44 +/- 21 percent in the lovastatin group (P = 0.50) [4].
  • We now show that treatment of cells with lovastatin, which inhibits modification of small GTP-binding proteins, reduced PIP2 levels and decreased calcium mobilization in response to PDGF and thrombin [13].

Chemical compound and disease context of lovastatin


Biological context of lovastatin

  • A broad spectrum of Cdk-inhibitory activity associated with a 28-kilodalton protein (p28lck1) was induced in cells treated with the drug lovastatin or upon density-mediated growth arrest and was periodic in the cell cycle, with peak activity in G1 [19].
  • OBJECTIVE: To assess the lipid-lowering efficacy, biochemical safety, and effect on growth and sexual development of lovastatin in adolescent boys with HeFH [20].
  • Growth and sexual maturation assessed by Tanner staging and testicular volume were not significantly different between the lovastatin and placebo groups at 24 weeks (P = .85) and 48 weeks (P = .33); neither were serum hormone levels or biochemical parameters of nutrition [20].
  • Thus, a low dose of lovastatin appears highly effective for treatment of moderate hypercholesterolemia in most postmenopausal women, presumably because it reverses the reduction in LDL receptor activity associated with menopause [21].
  • The isoprenoid end product isopentenyl adenine (5 or 50 microM) had little effect on DNA synthesis and cell proliferation in lovastatin-blocked cells [22].

Anatomical context of lovastatin


Associations of lovastatin with other chemical compounds


Gene context of lovastatin

  • Further analysis demonstrated that Cx26 is a cell-cycle regulated gene expressed at a moderate level during G1 and S, and strongly up-regulated in late S and G2, as shown with lovastatin-synchronized NMECs [30].
  • Our study suggests that lovastatin, alone or in combination with a MEK1 inhibitor, may represent a new and immediately available therapeutic approach to combat tumors with activated ERK1/2, such as AML [31].
  • We show that p38 and c-Jun NH2-terminal kinase/stress-activated kinase MAPK pathways are not altered during lovastatin-induced apoptosis [31].
  • Up-regulation of LDL receptors by lovastatin treatment of normal human foreskin fibroblasts (FSF cells) resulted in an increase in LPL-induced VLDL binding and catabolism to a level that was 10-15-fold greater than in LDL receptor-negative fibroblasts, despite similar LRP activity in both cell lines [32].
  • By using p21 promoter deletion constructs, the lovastatin-responsive element was mapped to a region between -93 and -64 relative to the transcription start site [33].

Analytical, diagnostic and therapeutic context of lovastatin


  1. The efficacy of intensive dietary therapy alone or combined with lovastatin in outpatients with hypercholesterolemia. Hunninghake, D.B., Stein, E.A., Dujovne, C.A., Harris, W.S., Feldman, E.B., Miller, V.T., Tobert, J.A., Laskarzewski, P.M., Quiter, E., Held, J. N. Engl. J. Med. (1993) [Pubmed]
  2. Rhabdomyolysis in patients receiving lovastatin after cardiac transplantation. East, C., Alivizatos, P.A., Grundy, S.M., Jones, P.H., Farmer, J.A. N. Engl. J. Med. (1988) [Pubmed]
  3. Lovastatin for lowering cholesterol levels in non-insulin-dependent diabetes mellitus. Garg, A., Grundy, S.M. N. Engl. J. Med. (1988) [Pubmed]
  4. Lack of effect of lovastatin on restenosis after coronary angioplasty. Lovastatin Restenosis Trial Study Group. Weintraub, W.S., Boccuzzi, S.J., Klein, J.L., Kosinski, A.S., King, S.B., Ivanhoe, R., Cedarholm, J.C., Stillabower, M.E., Talley, J.D., DeMaio, S.J. N. Engl. J. Med. (1994) [Pubmed]
  5. Myolysis and acute renal failure in a heart-transplant recipient receiving lovastatin. Norman, D.J., Illingworth, D.R., Munson, J., Hosenpud, J. N. Engl. J. Med. (1988) [Pubmed]
  6. Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults. Muldoon, M.F., Ryan, C.M., Sereika, S.M., Flory, J.D., Manuck, S.B. Am. J. Med. (2004) [Pubmed]
  7. Atherogenic risk reduction in patients with dyslipidaemia. comparison between bezafibrate and lovastatin. Sinzinger, H., Pirich, C., Kondor, P., Etti, H. Eur. Heart J. (1995) [Pubmed]
  8. Lovastatin modulation of microglial activation via suppression of functional CD40 expression. Townsend, K.P., Shytle, D.R., Bai, Y., San, N., Zeng, J., Freeman, M., Mori, T., Fernandez, F., Morgan, D., Sanberg, P., Tan, J. J. Neurosci. Res. (2004) [Pubmed]
  9. Safety and compliance with once-daily niacin extended-release/lovastatin as initial therapy in the Impact of Medical Subspecialty on Patient Compliance to Treatment (IMPACT) study. Rubenfire, M. Am. J. Cardiol. (2004) [Pubmed]
  10. Comparison of effects on sleep of lovastatin and pravastatin in hypercholesterolemia. Partinen, M., Pihl, S., Strandberg, T., Vanhanen, H., Murtomäki, E., Block, G., Neafus, R., Haigh, J., Miettinen, T., Reines, S. Am. J. Cardiol. (1994) [Pubmed]
  11. Lovastatin for X-linked adrenoleukodystrophy. Singh, I., Khan, M., Key, L., Pai, S. N. Engl. J. Med. (1998) [Pubmed]
  12. Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. Treasure, C.B., Klein, J.L., Weintraub, W.S., Talley, J.D., Stillabower, M.E., Kosinski, A.S., Zhang, J., Boccuzzi, S.J., Cedarholm, J.C., Alexander, R.W. N. Engl. J. Med. (1995) [Pubmed]
  13. The small GTP-binding protein Rho regulates a phosphatidylinositol 4-phosphate 5-kinase in mammalian cells. Chong, L.D., Traynor-Kaplan, A., Bokoch, G.M., Schwartz, M.A. Cell (1994) [Pubmed]
  14. Myopathy and rhabdomyolysis associated with lovastatin-gemfibrozil combination therapy. Pierce, L.R., Wysowski, D.K., Gross, T.P. JAMA (1990) [Pubmed]
  15. Treatment of primary moderate hypercholesterolemia with lovastatin (mevinolin) and colestipol. Vega, G.L., Grundy, S.M. JAMA (1987) [Pubmed]
  16. Plasma mevalonate response in lovastatin-related myopathy. Maher, V.M., Pappu, A., Illingworth, D.R., Thompson, G.R. Lancet (1989) [Pubmed]
  17. 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors reduce human pancreatic cancer cell invasion and metastasis. Kusama, T., Mukai, M., Iwasaki, T., Tatsuta, M., Matsumoto, Y., Akedo, H., Inoue, M., Nakamura, H. Gastroenterology (2002) [Pubmed]
  18. Lovastatin augments sulindac-induced apoptosis in colon cancer cells and potentiates chemopreventive effects of sulindac. Agarwal, B., Rao, C.V., Bhendwal, S., Ramey, W.R., Shirin, H., Reddy, B.S., Holt, P.R. Gastroenterology (1999) [Pubmed]
  19. Translational control of p27Kip1 accumulation during the cell cycle. Hengst, L., Reed, S.I. Science (1996) [Pubmed]
  20. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia: a randomized controlled trial. Stein, E.A., Illingworth, D.R., Kwiterovich, P.O., Liacouras, C.A., Siimes, M.A., Jacobson, M.S., Brewster, T.G., Hopkins, P., Davidson, M., Graham, K., Arensman, F., Knopp, R.H., DuJovne, C., Williams, C.L., Isaacsohn, J.L., Jacobsen, C.A., Laskarzewski, P.M., Ames, S., Gormley, G.J. JAMA (1999) [Pubmed]
  21. Hypercholesterolemia in postmenopausal women. Metabolic defects and response to low-dose lovastatin. Arca, M., Vega, G.L., Grundy, S.M. JAMA (1994) [Pubmed]
  22. Lovastatin inhibits proliferation of rat mesangial cells. O'Donnell, M.P., Kasiske, B.L., Kim, Y., Atluru, D., Keane, W.F. J. Clin. Invest. (1993) [Pubmed]
  23. HMG-CoA reductase mediates the biological effects of retinoic acid on human neuroblastoma cells: lovastatin specifically targets P-glycoprotein-expressing cells. Dimitroulakos, J., Yeger, H. Nat. Med. (1996) [Pubmed]
  24. Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. Pahan, K., Sheikh, F.G., Namboodiri, A.M., Singh, I. J. Clin. Invest. (1997) [Pubmed]
  25. Cardiovascular effects of acute hypercholesterolemia in rabbits. Reversal with lovastatin treatment. Osborne, J.A., Lento, P.H., Siegfried, M.R., Stahl, G.L., Fusman, B., Lefer, A.M. J. Clin. Invest. (1989) [Pubmed]
  26. Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a). Maher, V.M., Brown, B.G., Marcovina, S.M., Hillger, L.A., Zhao, X.Q., Albers, J.J. JAMA (1995) [Pubmed]
  27. Comparison of lovastatin and gemfibrozil in normolipidemic patients with hypoalphalipoproteinemia. Vega, G.L., Grundy, S.M. JAMA (1989) [Pubmed]
  28. 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]
  29. Acetaldehyde impairs mitochondrial glutathione transport in HepG2 cells through endoplasmic reticulum stress. Lluis, J.M., Colell, A., García-Ruiz, C., Kaplowitz, N., Fernández-Checa, J.C. Gastroenterology (2003) [Pubmed]
  30. Transcriptional downregulation of gap-junction proteins blocks junctional communication in human mammary tumor cell lines. Lee, S.W., Tomasetto, C., Paul, D., Keyomarsi, K., Sager, R. J. Cell Biol. (1992) [Pubmed]
  31. Blocking the Raf/MEK/ERK pathway sensitizes acute myelogenous leukemia cells to lovastatin-induced apoptosis. Wu, J., Wong, W.W., Khosravi, F., Minden, M.D., Penn, L.Z. Cancer Res. (2004) [Pubmed]
  32. Lipoprotein lipase binds to low density lipoprotein receptors and induces receptor-mediated catabolism of very low density lipoproteins in vitro. Medh, J.D., Bowen, S.L., Fry, G.L., Ruben, S., Andracki, M., Inoue, I., Lalouel, J.M., Strickland, D.K., Chappell, D.A. J. Biol. Chem. (1996) [Pubmed]
  33. Inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase pathway induces p53-independent transcriptional regulation of p21(WAF1/CIP1) in human prostate carcinoma cells. Lee, S.J., Ha, M.J., Lee, J., Nguyen, P., Choi, Y.H., Pirnia, F., Kang, W.K., Wang, X.F., Kim, S.J., Trepel, J.B. J. Biol. Chem. (1998) [Pubmed]
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