fluvastatin   Click here for help

GtoPdb Ligand ID: 2951

Synonyms: Canef® | Lescol®
Approved drug PDB Ligand
fluvastatin is an approved drug (FDA (1993))
Compound class: Synthetic organic
Comment: Fluvastatin is a member of the cholesterol-lowering statin family of drugs. The approved drug is a racemic mixture of a 3R, 5S isomer and a 3S, 5R isomer, and this is supported by the INN document which also indicates a racemate. The 3R, 5S isomer (shown here, and in the PubChem link below) is more pharmacologically active [1,4]. The other isomer is represented by CID 1548972. Representations of the stereochemistry of fluvastatin shown on the resources linked to below may vary from the structure shown here. The majority of the references we cite for our biological activity data do not specify whether the racemate or a specific stereoisomer were used in their experiments.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

IUPHAR Pharmacology Education Project (PEP) logo

View more information in the IUPHAR Pharmacology Education Project: fluvastatin

fluvastatin is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 82.69
Molecular weight 411.18
XLogP 4.51
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES OC(=O)CC(CC(C=Cc1c(c2ccc(cc2)F)c2c(n1C(C)C)cccc2)O)O
Isomeric SMILES OC(=O)C[C@@H](C[C@@H](/C=C/c1c(c2ccc(cc2)F)c2c(n1C(C)C)cccc2)O)O
InChI InChI=1S/C24H26FNO4/c1-15(2)26-21-6-4-3-5-20(21)24(16-7-9-17(25)10-8-16)22(26)12-11-18(27)13-19(28)14-23(29)30/h3-12,15,18-19,27-28H,13-14H2,1-2H3,(H,29,30)/b12-11+/t18-,19-/m1/s1
InChI Key FJLGEFLZQAZZCD-MCBHFWOFSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Boralli VB, Coelho EB, Sampaio SA, Marques MP, Lanchote VL. (2009)
Enantioselectivity in the pharmacokinetic interaction between fluvastatin and lercanidipine in healthy volunteers.
J Clin Pharmacol, 49 (2): 205-11. [PMID:19033449]
2. Carbonell T, Freire E. (2005)
Binding thermodynamics of statins to HMG-CoA reductase.
Biochemistry, 44 (35): 11741-8. [PMID:16128575]
3. Connolly PJ, Westin CD, Loughney DA, Minor LK. (1993)
HMG-CoA reductase inhibitors: design, synthesis, and biological activity of tetrahydroindazole-substituted 3,5-dihydroxy-6-heptenoic acid sodium salts.
J Med Chem, 36 (23): 3674-85. [PMID:8246237]
4. Di Pietro G, Coelho EB, Geleilete TM, Marques MP, Lanchote VL. (2006)
Chiral evaluation of fluvastatin in human plasma by high-performance liquid chromatography electrospray mass spectrometry.
J Chromatogr B Analyt Technol Biomed Life Sci, 832 (2): 256-61. [PMID:16480934]
5. Holdgate GA, Ward WH, McTaggart F. (2003)
Molecular mechanism for inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase by rosuvastatin.
Biochem Soc Trans, 31 (Pt 3): 528-31. [PMID:12773150]
6. Hosoda S, Matsuda D, Tomoda H, Hashimoto M, Aoyama H, Hashimoto Y. (2009)
Application of a 3,3-diphenylpentane skeleton as a multi-template for creation of HMG-CoA reductase inhibitors.
Bioorg Med Chem Lett, 19 (15): 4228-31. [PMID:19502059]
7. Istvan ES, Deisenhofer J. (2001)
Structural mechanism for statin inhibition of HMG-CoA reductase.
Science, 292 (5519): 1160-4. [PMID:11349148]
8. Jendralla H, Granzer E, von Kerekjarto B, Krause R, Schacht U, Baader E, Bartmann W, Beck G, Bergmann A, Kesseler K. (1991)
Synthesis and biological activity of new HMG-CoA reductase inhibitors. 3. Lactones of 6-phenoxy-3,5-dihydroxyhexanoic acids.
J Med Chem, 34 (10): 2962-83. [PMID:1656041]
9. McTaggart F, Buckett L, Davidson R, Holdgate G, McCormick A, Schneck D, Smith G, Warwick M. (2001)
Preclinical and clinical pharmacology of Rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.
Am J Cardiol, 87 (5A): 28B-32B. [PMID:11256847]