Mevastatin

Mevastatin (Compactin) is a first HMG-CoA reductase inhibitor that belongs to the statins class. Mevastatin is a lipid-lowering agent, and induces apoptosis, arrests cancer cells in G₀/G₁ phase. Mevastatin also increases endothelial nitric oxide synthase (eNOS) mRNA and protein levels. Mevastatin has antitumor activity and has the potential for cardiovascular diseases treatment^[1][2][3]. IC50 & Target:HMG-CoA reductase^[1][2]
Apoptosis^[1] In Vitro: Mevastatin (0-128 μM; 5 days; Caco-2 cells) treatment causes a dose-dependent decrease in cell number^[1].
Mevastatin (32-128 μM; 24-72 hours; Caco-2 cells) treatment causes an early G0/G1 phase and a late G2/M phase cell cyclr arrest^[1].
Mevastatin (32-128 μM; 72 hours; Caco-2 cells) treatment causes a down-regulation of cyclin-dependent kinases (cdk) 4 and cdk 6 as well as cyclin D1, while cdk 2 and cyclin E protein levels remained unchanged. Cell cycle inhibitors p21 and p27 are significantly upregulated by Mevastatin^[1].
Mevastatin (16-256 μM; Caco-2 cells) treatment induces apoptosis in a dose-dependent manner^[1].
Treatment of Neuro2a cells with mevastatin for 24 hours induced neurite outgrowth associated with up-regulation of the neuronal marker protein NeuN. Mevastatin triggers phosphorylation of the key kinases epidermal growth factor receptor (EGFR), ERK1/2, and Akt/protein kinase B. Inhibition of EGFR, PI3K, and the mitogen-activated protein kinase cascade blocks Mevastatin-induced neurite outgrowth^[4]. In Vivo: Mevastatin (2-20 mg/kg; delivered via ALZET miniosmotic pumps; daily; for 7, 14, or 28 days; wild-type 129-SV/eVTAcBr male mice and eNOS-deficient male mice) treatment increases levels of endothelial nitric oxide synthase (eNOS) mRNA and protein, reduces infarct size, and improves neurological deficits in a dose- and time-dependent manner^[2].
The topical infusion of Mevastatin (2.5 pmol/hr) increases bone mass (MRL/MpJ mouse) of isografted bone by increasing bone turnover and, at least in part, by promoting the expression of bone morphogenetic protein-2 (BMP-2) mRNA and receptor activator of NF-κB ligand (RANKL) mRNA^[3].