product name Mevastatin
Description: Mevastatin, also known as CS-500 and ML-236B, is a competitive inhibitor of HMG-Coenzyme A (HMG-CoA) reductase with a binding affinity 10,000 times greater than the native HMG-CoA substrate itself. Mevastatin is a hypolipidemic agent that belongs to the statins class and was isolated from the mold Penicillium citrinum by Akira Endo in the 1970s, and he identified it as a HMG-CoA reductase inhibitor, i.e., a statin. Mevastatin is considered to be the first statin drug but it was never marketed due to toxicities.
References: J Antibiot (Tokyo). 1976 Dec;29(12):1346-8; Stroke. 2001 Apr;32(4):980-6.
390.51
Formula
C23H34O5
CAS No.
73573-88-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 78 mg/mL (199.7 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
ML-236B
other peoduct :
| In Vitro |
In vitro activity: Mevastatin is a cholesterol-lowering agent isolated from Penicillium citinium. It reduces cholesterol synthesis to 50% of control at 0.01 pg/mL (26 nM). It is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Mevastatin is a prodrug that is activated in vivo via hydrolysis of the lactone ring. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind with 10,000 times greater affinity than its natural substrate. The bicyclic portion of mevastatin binds to the coenzyme A portion of the active site. Mevastatin increases levels of eNOS mRNA and protein, reduces infarct size, and improves neurological deficits in a dose- and time-dependent manner. Kinase Assay: Mevastatin inhibits HMG-CoA reductase reversibly and competes with HMG-CoA. It shows a Ki value of about 1nM. Cell Assay: Mevastatin inhibits sterol synthesis from acetate in various cells at low concentration of nanomolar. It also inhibits acetate incorporation with IC50 value of 1nM. Besides that, mevastatin completely suppresses the growth of L cells at 1.3μM. Mevastatin is also found to affect the cell cycle and change cell morphology in cultured fibroblasts. |
|---|---|
| In Vivo | At doses of 5 and 20 mg/kg, mevastatin produces reduction of serum cholesterol levels at 3 hours after oral administration. It lowers the levels of serum cholesterol by approximately 30 % at a dose of 20 mg/kg. Mevastatin lowers hepatic production of cholesterol by competitively inhibiting HMG-CoA reductase. Cholesterol levels are reduced only after 28 days of treatment and does not correlate with infarct reduction. Baseline absolute cerebral blood flow is 30% higher after 14-day high-dose treatment. |
| Animal model | Wistar-Imamichi male rats |
| Formulation & Dosage | Dissolved in saline; 5, 20 mg/kg; p.o. |
| References | J Antibiot (Tokyo). 1976 Dec;29(12):1346-8; Stroke. 2001 Apr;32(4):980-6. |
