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| Name | Cerivastatin | ||||||||||||||||||||||||||||||||||||||||||
| Accession Number | DB00439 (APRD00102) | ||||||||||||||||||||||||||||||||||||||||||
| Type | small molecule | ||||||||||||||||||||||||||||||||||||||||||
| Groups | withdrawn | ||||||||||||||||||||||||||||||||||||||||||
| Description | On August 8, 2001 the U.S. Food and Drug Administration (FDA) announced that Bayer Pharmaceutical Division voluntarily withdrew Baycol from the U.S. market, due to reports of fatal Rhabdomyolysis, a severe adverse reaction from this cholesterol-lowering (lipid-lowering) product. It has also been withdrawn from the Canadian market. |
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| Structure |
Download: MOL | SDF | SMILES | InChI Display: 2D Structure | 3D Structure |
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| Salts | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| Brand mixtures | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| CAS number | 145599-86-6 | ||||||||||||||||||||||||||||||||||||||||||
| Weight |
Average: 459.5503 Monoisotopic: 459.242101408 |
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| Chemical Formula | C26H34FNO5 | ||||||||||||||||||||||||||||||||||||||||||
| InChI Key | InChIKey=SEERZIQQUAZTOL-ANMDKAQQSA-N | ||||||||||||||||||||||||||||||||||||||||||
| InChI |
InChI=1S/C26H34FNO5/c1-15(2)25-21(11-10-19(29)12-20(30)13-23(31)32)24(17-6-8-18(27)9-7-17)22(14-33-5)26(28-25)16(3)4/h6-11,15-16,19-20,29-30H,12-14H2,1-5H3,(H,31,32)/b11-10+/t19-,20-/m1/s1
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| IUPAC Name |
(3R,5S,6E)-7-[4-(4-fluorophenyl)-5-(methoxymethyl)-2,6-bis(propan-2-yl)pyridin-3-yl]-3,5-dihydroxyhept-6-enoic acid
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| SMILES |
COCC1=C(C2=CC=C(F)C=C2)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C(C(C)C)N=C1C(C)C
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| Mass Spec | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Taxonomy | |||||||||||||||||||||||||||||||||||||||||||
| Kingdom | Organic | ||||||||||||||||||||||||||||||||||||||||||
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| Substructures |
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| Pharmacology | |||||||||||||||||||||||||||||||||||||||||||
| Indication | Used as an adjunct to diet for the reduction of elevated total and LDL cholesterol levels in patients with primary hypercholesterolemia and mixed dyslipidemia (Fredrickson Types IIa and IIb) when the response to dietary restriction of saturated fat and cholesterol and other non-pharmacological measures alone has been inadequate. | ||||||||||||||||||||||||||||||||||||||||||
| Pharmacodynamics | Cerivastatin, a competitive HMG-CoA reductase inhibitor effective in lowering LDL cholesterol and triglycerides, is used to treat primary hypercholesterolemia and mixed dyslipidemia (Fredrickson types IIa and IIb). | ||||||||||||||||||||||||||||||||||||||||||
| Mechanism of action | Cerivastatin competitively inhibits hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the hepatic enzyme responsible for converting HMG-CoA to mevalonate. As mevalonate is a precursor of sterols such as cholesterol, this results in a decrease in cholesterol in hepatic cells, upregulation of LDL-receptors, and an increase in hepatic uptake of LDL-cholesterol from the circulation. | ||||||||||||||||||||||||||||||||||||||||||
| Absorption | The mean absolute oral bioavailability 60% (range 39 - 101%). | ||||||||||||||||||||||||||||||||||||||||||
| Volume of distribution | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Protein binding | More than 99% of the circulating drug is bound to plasma proteins (80% to albumin). | ||||||||||||||||||||||||||||||||||||||||||
| Metabolism | Hepatic. Biotransformation pathways for cerivastatin in humans include the following: demethylation of the benzylic methyl ether to form Ml and hydroxylation of the methyl group in the 6'-isopropyl moiety to form M23. | ||||||||||||||||||||||||||||||||||||||||||
| Route of elimination | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Half life | 2-3 hours | ||||||||||||||||||||||||||||||||||||||||||
| Clearance | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| Toxicity | Rhabdomyolysis, liver concerns | ||||||||||||||||||||||||||||||||||||||||||
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| Prices | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| Properties | |||||||||||||||||||||||||||||||||||||||||||
| State | solid | ||||||||||||||||||||||||||||||||||||||||||
| Experimental Properties |
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| Synthesis Reference | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| General Reference |
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| ATC Codes |
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| AHFS Codes | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| PDB Entries | Not Available | ||||||||||||||||||||||||||||||||||||||||||
| FDA label | show (144 KB) | ||||||||||||||||||||||||||||||||||||||||||
| MSDS | Not Available | ||||||||||||||||||||||||||||||||||||||||||
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| Drug Interactions |
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| Targets |
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1. 3-hydroxy-3-methylglutaryl-coenzyme A reductase Pharmacological action: yesActions: inhibitor This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis Organism class: humanUniProt ID: P04035 ![]() Gene: HMGCR ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Enzymes |
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Actions: substrate, inhibitor, inducer
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684![]() Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics UniProt ID: P20815![]() Gene: CYP3A5 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics UniProt ID: P24462![]() Gene: CYP3A7 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: substrate, inhibitor
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti- cancer drug paclitaxel (taxol) UniProt ID: P10632![]() Gene: CYP2C8 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: inhibitor
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants UniProt ID: P10635![]() Gene: CYP2D6 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: inhibitor
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine UniProt ID: P33261![]() Gene: CYP2C19 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: inhibitor, inducer
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan UniProt ID: P11712![]() Gene: CYP2C9 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
Actions: inducer
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics UniProt ID: P20813![]() Gene: CYP2B6 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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| Transporters |
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1. Multidrug resistance protein 1 Actions: substrateEnergy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183![]() Gene: ABCB1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
2. Canalicular multispecific organic anion transporter 1 Actions: substrateMediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter UniProt ID: Q92887![]() Gene: ABCC2 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
3. ATP-binding cassette sub-family G member 2 Actions: substrateXenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123 UniProt ID: Q9UNQ0![]() Gene: ABCG2 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
4. Solute carrier organic anion transporter family member 1B1 Actions: substrateMediates the Na(+)-independent transport of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostaglandin E2, thromboxane B2, leukotriene C3, leukotriene E4, thyroxine and triiodothyronine. May play an important role in the clearance of bile acids and organic anions from the liver UniProt ID: Q9Y6L6![]() Gene: SLCO1B1 ![]() Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report ![]() References:
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