Mevinolin from Aspergillus sp. 

Cholesterol lowering drug and competitive inhibitor of HMG-CoA reductase, a rate limiting enzyme in cholesterol synthesis. Blocks the production of mevalonate, a critical compound in the production of cholesterol and isoprenoids. This product is a substrate of Pgp and CYP3A. It increases cellular resistance to anticancer agents such as doxorubicin and induces apoptosis in myeloma cells. The roles of Pgp and CYP3A, possible connection between drug resistance, regulation of the mevalonate pathway, and iosprenylation of signaling proteins in these observations remain to be resolved. The product induces apoptosis in numerous cancer cell lines perhaps, in part, by inhibiting the isoprenylation of Rho family GTPases. It causes cell cycle arrest in G₁ and G₂/M phases.

≥98% (HPLC)

human ... HMGCR(3156)

rat ... Hmgcr(25675)

2-8°C

Alberts, A.W., et al., Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc. Natl. Acad. Sci. USA 77, 3957-3961, (1980) abstract

Ghosh, P.M., et al., Lovastatin induces apoptosis by inhibiting mitotic and post-mitotic events in cultured mesangial cells. Biochim. Biophys. Acta 1359, 13-24, (1997) abstract

van de Donk, N.W., et al., The cholesterol lowering drug lovastatin induces cell death in myeloma plasma cells. Leukemia 16, 1362-1371, (2002) abstract

Bardeleben, R.V., et al., The HMG-CoA reductase inhibitor lovastatin protects cells from the antineoplastic drugs doxorubicin and etoposide. Int. J. Mol. Med. 10, 473-479, (2002) abstract

Muller, C., et al., Lovastatin inhibits proliferation of pancreatic cancer cell lines with mutant as well as with wild-type K-ras oncogene but has different effects on protein phosphorylation and induction of apoptosis. Int. J. Oncol. 12, 717-723, (1998) abstract

Maksumova, L., et al., Increased sensitivity of multidrug-resistant myeloid leukemia cell lines to lovastatin. Leukemia 14, 1444-1450, (2000) abstract

Zhong, W.B., et al., Lovastatin induces apoptosis of anaplastic thyroid cancer cells via inhibition of protein geranylgeranylation and de novo protein synthesis. Endocrinology 144, 3852-3859, (2003) abstract

Agarwal, B., et al., Mechanism of lovastatin-induced apoptosis in intestinal epithelial cells. Carcinogenesis 23, 521-528, (2002) abstract

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EK7907000