(1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (2S)-2-methylbutanoate

• ChemBase ID: 112
• Molecular Formular: C24H36O5
• Molecular Mass: 404.53964
• Monoisotopic Mass: 404.25627425
• SMILES: O([C@@H]1[C@@H]2[C@H]([C@H](C=CC2=C[C@@H](C1)C)C)CC[C@H]1OC(=O)C[C@H](O)C1)C(=O)[C@H](CC)C
• Canonical SMILES: CC[C@@H](C(=O)O[C@H]1C[C@@H](C)C=C2[C@H]1[C@@H](CC[C@@H]1C[C@@H](O)CC(=O)O1)[C@H](C=C2)C)C
• InChI: InChI=1S/C24H36O5/c1-5-15(3)24(27)29-21-11-14(2)10-17-7-6-16(4)20(23(17)21)9-8-19-12-18(25)13-22(26)28-19/h6-7,10,14-16,18-21,23,25H,5,8-9,11-13H2,1-4H3/t14-,15-,16-,18+,19+,20-,21-,23-/m0/s1
• InChIKey: PCZOHLXUXFIOCF-BXMDZJJMSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (2S)-2-methylbutanoate
• IUPAC Traditional name: (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (2S)-2-methylbutanoate; lovastatin
• Brand Name: Altocor; Altoprev; Artein; Belvas; Cholestra; Closterol; Colevix; Hipolip; Hipovastin; Lestatin; Lipdip; Lipivas; Lipofren; Lovalip; Lovalord; Lovasterol; Lovastin; Lozutin; Mevacor; Mevinacor; Mevlor; Monacolin K; Nergadan; Paschol; Rodatin; Rovacor; Sivlor; Taucor; Tecnolip; Teroltrat
• Synonyms: 8-[2-(4-Hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethy l]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthale; 2-Methyl-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester butanoic acid; 6-α-Methylcompactin; Monacolin K; Mevinolin from Aspergillus sp.; (2S)-2-Methylbutanoic Acid (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2-[(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-1-naphthalenyl Ester; (+)-Mevinolin; 6α-Methylcompactin; Altocor; Antibiotic MB 530B; L 154803; Lostatin; Lovalip; Lovastatin Lactone; MK 803; MSD 803; Mevacor; Mevinacor; Mevinolin; Mevlor; Monacolin K Lactone; Sivlor; Lipofren; Nergadan; Tancor; lovastatin; Lovastatina [Spanish]; Lovastatine [French]; Lovastatinum [Latin]; 6 alpha-Methylcompactin; lovastatin; Lovastatin; (S)-(1S,3R,7S,8S,8aR)-8-(2-((2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2-methylbutanoate; (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (2S)-2-methylbutanoate; 洛伐司他汀

Database IDs

• CAS Number: 75330-75-5
• MDL Number: MFCD00072164
• PubChem SID: 46508223; 160963575; 24896706
• PubChem CID: 53232
• CHEBI ID: 40303
• ATC CODE: C10AA02
• CHEMBL: 503
• Chemspider ID: 48085
• DrugBank ID: DB00227
• IUPHAR ligand ID: 2739
• KEGG ID: D00359
• Unique Ingredient Identifier: 9LHU78OQFD
• Wikipedia Title: Lovastatin
• Medline Plus: a688006

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.914537
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 3.9021869
• LogD (pH = 7.4): 3.9021869
• Log P: 3.9021869
• Molar Refractivity: 113.1824 cm^3
• Polarizability: 44.4169 Å^3
• Polar Surface Area: 72.83 Å^2
• Rotatable Bonds: 7
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 4.11
• LOG S: -4.22
• Solubility (Water): 2.43e-02 g/l

PROPERTIES

Physical Property

• Solubility: 0.0004 mg/mL; Chloroform; DMSO; Hot Methanol
• Apperance: White Solid
• Melting Point: 152-154°C; 166 - 168°C; 175°C
• Hydrophobicity(logP): 4.082; 4.5

Safety Information

• Storage Condition: -20°C Freezer
• Storage Warning: IRRITANT
• RTECS: EK7907000
• European Hazard Symbols: X
• German water hazard class: 3
• Risk Statements: 22-36/37/38
• Safety Statements: 26-36/37
• TSCA Listed: false; 否
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302; H302-H315-H319-H335
• GHS Precautionary statements: P261-P305+P351+P338-P302+P352-P321-P405-P501A
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Storage Temperature: 2-8°C

Pharmacology Properties

• Admin Routes: oral
• Bioavailability: <5%
• Excretion: negligible
• Half Life: 1.1-1.7 hours
• Metabolism: hepatic (CYP3A substrate)
• Protein Bound: >95%
• Legal Status: Rx-only (US)
• Pregnancy Category: X (US)
• Gene Information: human ... HMGCR(3156)rat ... Hmgcr(25675)
• Mechanism of Action: Inhibitor of cholesterol biosynthesis; Potent inhibitor of HMG-CoA

Product Information

• Purity: ≥98% (HPLC); 95%; 97%
• Biological Source: Metab. of Aspergillus terreus and Monascus ruber
• Application(s): Antihyperlipidaemic agent
• Quality Level: PREMIUM
• Empirical Formula (Hill Notation): C24H36O5

DETAILS

DrugBank - DB00227

• Drug Groups: approved; investigational
• Description: Lovastatin is a cholesterol-lowering agent that belongs to the class of medications called statins. It was the second agent of this class discovered. It was discovered by Alfred Alberts and his team at Merck in 1978 after screening only 18 compounds over 2 weeks. The agent, also known as mevinolin, was isolated from the fungi Aspergillus terreus. Research on this compound was suddenly shut down in 1980 and the drug was not approved until 1987. Interesting, Akira Endo at Sankyo Co. (Japan) patented lovastatin isolated from Monascus ruber four months before Merck. Lovastatin was found to be 2 times more potent than its predecessor, mevastatin, the first discovered statin. Like mevastatin, lovastatin is structurally similar to hydroxymethylglutarate (HMG), a substituent of HMG-Coenzyme A (HMG-CoA), a substrate of the cholesterol biosynthesis pathway via the mevalonic acid pathway. Lovastatin is a competitive inhibitor of HMG-CoA reductase with a binding affinity 20,000 times greater than HMG-CoA. Lovastatin differs structurally from mevastatin by a single methyl group at the 6’ position. Lovastatin is a prodrug that is activated by in vivo hydrolysis of the lactone ring. It, along with mevastatin, has served as one of the lead compounds for the development of the synthetic compounds used today.
• Indication: For management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia. For primary prevention of coronary heart disease and to slow progression of coronary atherosclerosis in patients with coronary heart disease.
• Pharmacology: The primary cause of cardiovascular disease is atherosclerotic plaque formation. Sustained elevations of cholesterol in the blood increase the risk of cardiovascular disease. Lovastatin lowers hepatic cholesterol synthesis by competitively inhibiting HMG-CoA reductase, the enzyme that catalyzes the rate-limiting step in the cholesterol biosynthesis pathway via the mevalonic acid pathway. Decreased hepatic cholesterol levels causes increased uptake of low density lipoprotein (LDL) cholesterol and reduces cholesterol levels in the circulation. At therapeutic doses, lovastatin decreases serum LDL cholesterol by 29-32%, increases high density lipoprotein (HDL) cholesterol by 4.6-7.3%, and decrease triglyceride levels by 2-12%. HDL cholesterol is thought to confer protective effects against CV disease, whereas high LDL and triglyceride levels are associated with higher risk of disease.
• Toxicity: LD₅₀>1000 mg/kg (orally in mice)
• Affected Organisms: Humans and other mammals
• Biotransformation: Undergoes first pass hydrolysis to active metabolites β-hydroxyacid and 6'-hydroxy dervative.
• Absorption: < 5%. Time to peak serum concentration is 2-4 hours.
• Half Life: 5.3 hours
• Protein Binding: > 95%
• Elimination: Lovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. 83% of the orally administered dose is excreted in bile and 10% is excreted in urine.
• References: Bobek P, Ozdin L, Galbavy S: Dose- and time-dependent hypocholesterolemic effect of oyster mushroom (Pleurotus ostreatus) in rats. Nutrition. 1998 Mar;14(3):282-6. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - M2147

Biochem/physiol Actions
Lovastatin is a 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.

Toronto Research Chemicals - L472225

An antihypercholesterolemic agent. A fungal metabolite, which is a potent inhibitor of HMG-CoA reductase.

REFERENCES

• Bobek P, Ozdin L, Galbavy S: Dose- and time-dependent hypocholesterolemic effect of oyster mushroom (Pleurotus ostreatus) in rats. Nutrition. 1998 Mar;14(3):282-6. Pubmed
• Bilheimer, D.W., et al.: Proc. Nat. Acad. Sci. USA, 80, 4124 (1983)
• Alberts et al (1980) Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc.Natl.Acad.Sci.USA 77 3957.