mevastatin   Click here for help

GtoPdb Ligand ID: 3031

Synonyms: compactin [2] | ML-236B [6]
PDB Ligand
Compound class: Synthetic organic
Comment: Mevastatin, originally isolated from Penicillium citrinum, was the first HMG-CoA reductase inhibitor (statin) to be identified [6].
Note, the structure presented here is a representative one, as there is some ambiguity in the stereoisomeric specification, see [2] and [5] for the primary references.
Click here for help

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.

✖

View interactive charts of activity data across species

mevastatin is commercially available from our sponsors

2D Structure
Click here for help

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.

✖
Click here for structure editor
Physico-chemical Properties
Click here for help

Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. 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.

✖
Hydrogen bond acceptors 5
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 72.83
Molecular weight 390.24
XLogP 4.07
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Click here for help

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.

✖
Canonical SMILES CCC(C(=O)OC1CCC=C2C1C(CCC1CC(O)CC(=O)O1)C(C=C2)C)C
Isomeric SMILES CC[C@@H](C(=O)O[C@H]1CCC=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/C23H34O5/c1-4-14(2)23(26)28-20-7-5-6-16-9-8-15(3)19(22(16)20)11-10-18-12-17(24)13-21(25)27-18/h6,8-9,14-15,17-20,22,24H,4-5,7,10-13H2,1-3H3/t14-,15-,17+,18+,19-,20-,22-/m0/s1
InChI Key AJLFOPYRIVGYMJ-INTXDZFKSA-N
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
hydroxymethylglutaryl-CoA reductase Rn Inhibitor Competitive 8.9 – 9.0 pKi - 4,7
⤷ pKi 9.0 (Ki 1x10-9 M) [4]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Assay used the acid form of mevastatin
pKi 8.9 (Ki 1.4x10-9 M) [7]
Conditions: Substrate concentrations: 20µM HMG CoA, 2.1 mM NADP
hydroxymethylglutaryl-CoA reductase Primary target of this compound Hs Inhibitor Competitive 7.6 pIC50 - 12
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [12]
Conditions: this is a modelling paper and data may have extracted from another source- please check
hydroxymethylglutaryl-CoA reductase Rn Inhibitor Competitive 5.9 – 8.0 pIC50 - 1,3,8-11
⤷ pIC50 8.0 (IC50 1x10-8 M) [11]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 3mM NADP, 0.2mM HMG-CoA. The sodium salt of compactin was tested using HMG-CoA enzyme purified from rat microsomal preparations.
pIC50 7.6 (IC50 2.5x10-8 M) [10]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Substrate concentrations: 0.45 µM HMG-CoA, 4mM NADPH
pIC50 7.5 (IC50 3x10-8 M) [9]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Inhibition of HMG-CoA reductase activity in partially purified rat liver
pIC50 7.4 (IC50 4x10-8 M) [8]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: DL-[3-14C]3-hydroxy-3-methylglutaryl-CoA (0.37 MBq) and 10 mg protein of microsomal fraction incubated at 37°C for 30 min The reaction was terminated by addition of 2 M HCl aq and the metabolites were converted to mevalonolactone. The metabolite mixture was separated by means of thin layer chromatography (Merck 20 TLC plates Silica Gel 60 F254) with acetone/benzene (1:1 v/v). The radioactivity of each spot on the plate was measured with a bioimaging analyzer (FLA-7000, Fuji Film, Japan).
pIC50 7.0 (IC50 1.1x10-7 M) [3]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Compactin (as a Na+ salt) was tested in an in vitro assay for the HMG-CoA reductase inhibitory activity in a microsomal preparation
pIC50 6.0 (IC50 1x10-6 M) [1]
Conditions: Inhibition of HMG-CoA reductase from rat liver
pIC50 6.0 (IC50 1x10-6 M) [1]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Inhibition of rat liver microsomal HMG-CoA reductase
pIC50 5.9 (IC50 1.15x10-6 M) [3]
Description: in vitro inhibition of HMG-CoA reductase
Conditions: Compactin (as lactone) was tested in an in vitro assay for the HMG-CoA reductase inhibitory activity in a microsomal preparation