Huagongshe화공사 화학 정보 인쇄 보고서 · 연구 참고용
로바스타틴
로바스타틴 · 로바스타틴(LOVASTATIN) · MONACOLIN K · MEVINOLIN · LOVASTATION · MK-803 · Lovastatin (Mevacor) · Lovastatin,Monacolin K
식별자 및 물리적 특성
| CAS No. | 75330-75-5 |
|---|---|
| 분자식 | C24H36O5 |
| 평균 분자량 | 404.5 g/mol |
| 단동위원소 질량 | 404.25627425 g/mol |
| SMILES | CC[C@H](C)C(=O)O[C@H]1C[C@@H](C)C=C2C=C[C@H](C)[C@H](CC[C@@H]3C[C@@H](O)CC(=O)O3)[C@H]21 |
| InChIKey | PCZOHLXUXFIOCF-BXMDZJJMSA-N |
| PubChem CID | 53232 |
| ChEMBL | CHEMBL152032 |
| ChEBI | CHEBI:40303 |
| EC No. | 616-212-7 |
| DTXSID | DTXSID5020784 |
| 현지명 | 로바스타틴 |
화학 및 물리적 성질
| XLogP | 4.3 |
|---|---|
| 극성 표면적 | 72.8 |
| 수소 결합 공여자 수 | 1 |
| 수소 결합 수용자 수 | 5 |
| 회전 가능 결합 수 | 7 |
| 무거운 원자 수 | 29 |
| 형식 전하 | 0 |
| 복잡도 | 666 |
| 의약품 | Pharmaceuticals -> AntilipidemicsPharmaceuticals -> StatinsPharmaceuticals -> Listed in ZINC15 |
| LogP(분배 계수) | log Kow = 4.264.54.04 |
| Color/Form | White crystalsWhite crystals from acetone aqueousA white, non-hygroscopic crystalline powder |
| 용해도 | In water, 0.4X10-3 mg/mL at 25 °CInsoluble in waterSolubility at 25 °C (mg/mL): acetone 47, acetonitrile 28, n-butanol 7, iso-butanol 14, chloroform 350, N,N-dimethylformamide 90, ethanol 16, methanol 28, n-octanol 2, n-propanol 11, iso-propanol 20Practically insoluble in hexaneVery soluble in chloroformsoluble in dimethyl formamideslightly soluble in acetone, ethanol에탄올: 가용성9.80-10.20mg/mL, 투명, 무색 내지 희미한 노란색 |
| Human Drugs | Breast FeedingLactationMilk, HumanAnticholesteremic AgentsHydroxymethylglutaryl-CoA Reductase InhibitorsHypolipidemic AgentsFDA approved drugs -> Active ingredientLipid-lowering agents |
| Endocrine Disruptors | Potential endocrine disrupting compound |
| 녹는점 | 179 °CMP: 174.5 °C (under nitrogen)175°C |
| Optical Rotation | Specific optical rotation at 25 °C for D (sodium) line: +323 deg (c = 0.5 g in 100 ml acetonitrile) |
| Physical Description | Solid |
| Stability/Shelf Life | Stable under recommended storage conditions.Lovastatin tablets should be stored in well-closed, light-resistant containers at 5-30 °C. When stored under these conditions, the tablets are stable for 24 months after the date of manufacture. Lovastatin is sensitive to light. Following exposure to extreme light conditions, the drug is stable for 24 hours or 1 month when exposed to UV (approximately 3230 lux) or fluorescent (approximately 10,764 lux) light, respectively, at 28 °C in air. |
| Dissociation Constants | 13.49 |
| 끓는 점 | 559.2±50.0 °C(Predicted) |
| 밀도 | 1.12±0.1 g/cm3(Predicted) |
| 증기압 | 0Pa at 25℃ |
| 굴절률 | 320 ° (C=0.5, CH3CN) |
| 저장 조건 | -20°C |
| 물리적 상태 | 백색 내지 회백색 분말 |
| pKa(산도 계수) | 13.49±0.40(Predicted) |
| 색상 | 하얀색 |
| 용해도 | 25&C에서 0.0004mg/mL |
| Merck | 14,5586 |
| BCS Class | 2 |
| 안정성 | 제공된 대로 구매일로부터 2년 동안 안정적입니다. DMSO 또는 에탄올 용액은 -20°C에서 최대 2개월 동안 보관할 수 있습니다. |
| InChIKey | PCZOHLXUXFIOCF-BXMDZJJMSA-N |
| SMILES | [H][C@]12[C@H](C[C@@H](C)C=C1C=C[C@H](C)[C@@H]2CC[C@@H]3C[C@@H](O)CC(=O)O3)OC(=O)[C@@H](C)CC |
| LogP(분배 계수) | 4.260 |
| EPA | Lovastatin (75330-75-5) |
화학적 성질
White Solid
안전 및 규제
| GHS 분류 | This chemical does not meet GHS hazard criteria for 0.4% (1 of 247) of reports.DangerH302 (19%): Harmful if swallowed [Warning Acute toxicity, oral]P203, P260, P261, P264, P270, P272, P280, P301+P317, P302+P352, P318, P319, P321, P330, P333+P317, P362+P364, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 247 reports by companies from 18 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies. |
|---|---|
| 규제 정보 | Hazard Traits - Developmental ToxicityRegulation (EC) No 178/2002 (amended)Status: Active Update: 03-09-2012 https://echa.europa.eu/registration-dossier/-/registered-dossier/10864Butanoic acid, 2-methyl-, (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-ylethyl-1-naphthalenyl ester, (2S)-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right. |
| FDA 요건 | The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including lovastatin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. |
| Toxic Combustion Products | Special hazards arising from the substance or mixture: Carbon oxides. |
| Hazard Classes and Categories | Acute Tox. 4 (19%)Acute Tox. 4 (100%) |
| Hazardous Reactivities and Incompatibilities | Incompatible materials: Strong oxidizing agents. |
| 소화 절차 | Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.Advice for firefighters: Wear self contained breathing apparatus for fire fighting if necessary. |
| 보관 조건 | Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 °C.Store at 20 deg to 25 °C (68 deg to 77 °F). Lovastatin Tablets USP must be protected from light. |
| 정리 방법 | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. |
| 처리 방법 | SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.Product: Offer surplus and non-recyclable solutions to a licensed disposal companyContaminated packaging: Dispose of as unused product. |
| Preventive Measures | ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. Environmental precautions: Do not let product enter drains.Precautions for safe handling: Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed.Appropriate engineering controls: Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday.Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker. |
| Personal Protective Equipment (PPE) | Eye/face protection: Safety glasses with side-shields conforming to EN166. Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).Skin protection: Handle with gloves.Body Protection: Complete suit protecting against chemicals. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace.Respiratory protection: For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator. For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). |
| 상호 작용 | ... A 60-year-old black man developed rhabdomyolysis after receiving lovastatin for 14 months. Rhabdomyolysis developed in the absence of other medications previously reported to cause this adverse effect when administered concomitantly with lovastatin. Adverse drug reaction causality algorithms categorized this reaction as either possible or probable. Rhabdomyolysis is an uncommon adverse effect associated with lovastatin therapy. Although reported cases of lovastatin-induced rhabdomyolysis were associated with the coadministration of cyclosporine, erythromycin, gemfibrozil, or nicotinic acid, this adverse effect may occur in the absence of these agents.Combined drug therapy should be approached with caution as information from controlled studies is limited. Based on post-marketing surveillance, gemfibrozil, other fibrates and lipid lowering doses of niacin (nicotinic acid) may increase the risk of myopathy when given concomitantly with HMG-CoA reductase inhibitors, probably because they can produce myopathy when given alone. Therefore, combined drug therapy should be approached with caution.Grapefruit juice contains one or more components that inhibit CYP3A4 and can increase the plasma levels of drugs metabolized by CYP3A4. The effect of typical consumption (one 250-ml glass daily) is minimal (34% increase in active plasma HMG-CoA reductase inhibitory activity as measured by the area under the concentration-time curve) and of no clinical relevance. However, because larger quantities (over 1 liter daily) significantly increase the plasma levels of HMG-CoA reductase inhibitory activity, grapefruit juice should be avoided during lovastatin therapy.Lovastatin, like several other inhibitors of HMG-CoA reductase, is a substrate of cytochrome P450 3A4 (CYP3A4). Certain drugs which inhibit this metabolic pathway can raise the plasma levels of lovastatin and may increase the risk of myopathy. These include itraconazole, ketoconazole, posaconazole, voriconazole, the macrolide antibiotics erythromycin and clarithromycin, the ketolide antibiotic telithromycin, HIV protease inhibitors, boceprevir, telaprevir, the antidepressant nefazodone, or cobicistat-containing products. Combination of these drugs with lovastatin is contraindicated. If short-term treatment with strong CYP3A4 inhibitors is unavoidable, therapy with lovastatin should be suspended during the course of treatmentFor more Interactions (Complete) data for Lovastatin (20 total), please visit the HSDB record page. |
| Hepatotoxicity | Lovastatin therapy is associated with mild, asymptomatic and usually transient serum aminotransferase elevations. In summary analyses of large scale studies with prospective monitoring, ALT elevations above normal occurred in 3% to 5% of patients, but were above 3 times the upper limit of normal (ULN) in only 0.4% compared to 0.1% of placebo recipients. These elevations were more common with higher doses of lovastatin, being greater than 3 times ULN in 0.1% of patients receiving 20 mg daily, 0.9% with 40 mg and 1.5% with 80 mg daily. Most of these elevations were self-limited and did not require dose modification, although discontinuation is recommended for any elevation above 10 times and for persistent elevations above 5 times the ULN. Lovastatin is also associated with frank, clinically apparent hepatic injury, but cases are rare. The onset of clinical injury ranges from a few weeks to several years. The pattern of injury is typically cholestatic, but can be hepatocellular. Rash, fever and eosinophilia are uncommon as are autoimmune features. The injury usually resolves rapidly upon stopping lovastatin, but instances of fatal acute liver failure and of prolonged cholestasis have been reported (Case 1). |
| 생태독성 수치 | EC50Species: Xenopus laevis (African Clawed Frog) blastulaConditions: freshwater, renewal, 23 °C, pH 6.5-9, hardness 16-400 mg/L CaCO3Concentration: 20500 ug/L for 96 hrEffect: development, increased deformation /98% purity/ |
| 환경 거동 | TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 7400(SRC), determined from a structure estimation method(2), indicates that lovastatin is expected to be immobile in soil(SRC). Volatilization of lovastatin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 2.1X10-10 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Lovastatin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.2X10-12 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2016).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 7400(SRC), determined from a structure estimation method(2), indicates that lovastatin is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 2.1X10-10 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 300(SRC), from its log Kow of 4.26(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is high(SRC). Biodegradation data in water were not available(SRC, 2016).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), lovastatin, which has an estimated vapor pressure of 2.2X10-12 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase lovastatin may be removed from the air by wet and dry deposition(SRC). Lovastatin contains chromophores that absorb UV light at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC). |
| 유해 작용 | Lovastatin is generally well tolerated with mild and transient adverse reactions. There are few reported cases of severe adverse effects associated with lovastatin. Below are the reported side effects of the drug: |
| 노출 경로 | Studies suggest that <5% of the oral dose reaches the general circulation as active inhibitors. Time to peak serum concentration is 2-4 hours. Lovastatin undergoes extensive first-pass metabolism so the availability of the drug in the system is low and variable. |
| 독성 요약 | IDENTIFICATION AND USE: Lovastatin is a white, non-hygroscopic crystalline powder. It is used for therapy as anticholesteremic agent, and Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor. HUMAN EXPOSURE AND TOXICITY: Lovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase above ten times the upper limit of normal. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma. There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including lovastatin. Treatment of HL-60 cells with lovastatin induced characteristic apoptosis in a dose-dependent manner. ANIMAL STUDIES: Lovastatin produced optic nerve degeneration (Wallerian degeneration of retinogeniculate fibers) in clinically normal dogs in a dose-dependent fashion starting at 60 mg/kg/day. Vestibulocochlear Wallerian-like degeneration and retinal ganglion cell chromatolysis were also seen in dogs treated for 14 weeks at 180 mg/kg/day. CNS vascular lesions, characterized by perivascular hemorrhage and edema, mononuclear cell infiltration of perivascular spaces, perivascular fibrin deposits and necrosis of small vessels, were seen in dogs treated with lovastatin at a dose of 180 mg/kg/day. In mice given oral lovastatin dosages of 100 or 500 mg/kg daily, an increase in the incidence of papilloma in the nonglandular mucosa of the stomach was observed. Since the glandular mucosa of the stomach in these rodents was not affected and the human stomach contains only glandular mucosa, the importance of this finding to humans is unclear. An increased incidence of hepatocellular carcinoma and adenoma was observed after 21 months in mice given oral lovastatin 500 mg/kg daily. Drug-related testicular atrophy, decreased spermatogenesis, spermatocytic degeneration and giant cell formation were seen in dogs starting at 20 mg/kg/day. Direct dosing of neonatal rats by subcutaneous injection with 10 mg/kg/day of the open hydroxyacid form of lovastatin resulted in delayed passive avoidance learning in female rats. Lovastatin has been shown to produce skeletal malformations in offspring of pregnant mice and rats dosed during gestation at 80 mg/kg/day. Lovastatin did not exhibit mutagenic potential in in vitro mammalian cell systems (rat or mouse hepatocytes, V-79 cell forward mutation study), in vitro (Chinese hamster ovary cell) or in vivo (mouse bone marrow) chromosomal aberration studies, or microbial (Ames test) systems with or without metabolic activation. There is some in vitro evidence, however, that inhibition of HMG-CoA reductase can inhibit DNA synthesis during the S phase of the cell life cyclethis inhibition appears to result from depletion of mevalonic acid and is independent of its conversion to cholesterol.Researchers gave a single 200 mg dose of lovastatin to 5 healthy volunteers, and no clinically significant adverse effects were reported. Cases of lovastatin overdose are reported, but none of the patients reported any specific symptoms. All the patients recovered without complications. The patient should discontinue lovastatin use if severe muscle symptoms or fatigue develop. CPK, creatinine, and urinalysis should be done to assess for myoglobinuria. Mild to moderate muscle symptoms should also call for discontinuation of lovastatin, pending a thorough investigation of symptoms.Lovastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Lovastatin is a prodrug that is activated <i>in vivo</i> via hydrolysis of the lactone ring to form the ‘_-hydroxyacid. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind to HMG-CoA reductase with 20,000 times greater affinity than its natural substrate. The bicyclic portion of lovastatin binds to the coenzyme A portion of the active site. |
| Ongoing Test Status | EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPAICSS Dashboard ApplicationAvailable from, as of December 8, 2016: http://actor.epa.gov/dashboard/] |
| Soil Adsorption/Mobility | Using a structure estimation method based on molecular connectivity indices(1), the Koc of lovastatin can be estimated to be 7400(SRC). According to a classification scheme(2), this estimated Koc value suggests that lovastatin is expected to be immobile in soil. |
| Natural Pollution Sources | Lovastatin has been isolated from Monascus ruber and Apergillus terreus(1), via fermentation(2,3). It can also obtained from the fungus Pleurotus ostreatus(4,5). Lovastatin is found in some red yeast rice productsred yeast rice is used as food in Chinese cuisine(6). |
| Human Toxicity Excerpts | /HUMAN EXPOSURE STUDIES/ Five healthy human volunteers have received up to 200 mg of lovastatin as a single dose without clinically significant adverse experiences./SIGNS AND SYMPTOMS/ Lovastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma./SIGNS AND SYMPTOMS/ There have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins, including lovastatin. If serious liver injury with clinical symptoms and/or hyperbilirubinemia or jaundice occurs during treatment with lovastatin, promptly interrupt therapy. If an alternate etiology is not found, do not restart lovastatin./CASE REPORTS/ ... A 60-year-old black man developed rhabdomyolysis after receiving lovastatin for 14 months. Rhabdomyolysis developed in the absence of other medications previously reported to cause this adverse effect when administered concomitantly with lovastatin. Adverse drug reaction causality algorithms categorized this reaction as either possible or probable. Rhabdomyolysis is an uncommon adverse effect associated with lovastatin therapy. Although reported cases of lovastatin-induced rhabdomyolysis were associated with the coadministration of cyclosporine, erythromycin, gemfibrozil, or nicotinic acid, this adverse effect may occur in the absence of these agents.For more Human Toxicity Excerpts (Complete) data for Lovastatin (20 total), please visit the HSDB record page. |
| Artificial Pollution Sources | Lovastatin's production and administration as a hypercholesterolemic drug(1) may result in its release to the environment through various waste streams(SRC). |
| 수질 위해 등급(WGK) | 3 |
| RTECS 번호 | EK7907000 |
| 운송 번호(UN) | 3077 |
| 독성 | LD50 orally in mice: >1000 mg/kg (Endo) |
| 관세 코드 | 29322090 |
| 위험 문구(R) | 36/37/38 |
| 위험 표시 | Xi |
| 안전 문구(S) | 22-24/25-36/37/39-26 |
| 포장분류 | III |
| 위험 등급 | 9Carc. 2Repr. 2 |
| 저장 분류 | 11 - Combustible Solids |
| 유해 물질 데이터 | 75330-75-5(Hazardous Substances Data) |
용도
개요
Lovastatin is an orally-active hypocholesterolemic useful in the treatment of familial hypercholesterolemia. The drug acts by inhibiting the HMG-CoA reductase-catalyzed rate limiting step of cholesterol biosynthesis. While treatment with lovastatin leads to significant reductions in total and LDL cholesterol, its effect on atherosclerosis or coronary heart disease has not been established.
역사
Statins are the most extensively used class of lipid-lowering medication. Lovastatin is the second statin discovered by scientists.Later, the official name lovastatin was established. The activity of lovastatin is much better than compactin.In July 1982, lovastatin showed dramatic effects on lowering LDL cholesterol in patients with severe hypercholesterolemia who were unresponsive to the existedmedicines, with very few adverse reactions .
용도
Lovastatin (mevinolin) is a metabolite first isolated from Monascus ruber and later found in several other fungal species. Lovastatin is a potent inhibitor of HMG-CoA. HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, responsible for the biosynthesis of cholesterol. Lovastatin was developed as a drug as a hypolipemic agent.
일반 설명
Lovastatin, 2-methylbutanoic acid 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester, mevinolin,MK-803 (Mevacor) (formerly called mevinolin), is a potentinhibitor of HMG-CoA. The drug was obtained originallyfrom the fermentation products of the fungi Aspergillus terreusand Monascus ruber. Lovastatin was one of two originalHMG-CoA reductase inhibitors. The other drug, mevastatin(formerly called compactin), was isolated from cultures ofPenicillium cillium citrum. Mevastatin was withdrawn fromclinical trials because it altered intestinal morphology in dogs.This effect was not observed with lovastatin. For inhibitoryeffects on HMG-CoA reductase, the lactone ring must be hydrolyzedto the open-ring heptanoic acid.