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ervogastat   Click here for help

GtoPdb Ligand ID: 12241

Synonyms: compound 6 [PMID: 34635855] | PF-06865571 | PF06865571
Compound class: Synthetic organic
Comment: Ervogastat (PF-06865571) is a diacylglycerol O-acyltransferase 2 (DGAT2) inhibitor [2]. DGAT2 inhibition is proposed as a mechanism to reduce hepatic triglyceride (TG) accumulation that underlies hepatic injury in non-alcoholic fatty liver disease.
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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
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 7
Hydrogen bond donors 1
Rotatable bonds 8
Topological polar surface area 108.35
Molecular weight 407.42
XLogP 0.93
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 CCOc1cccnc1Oc1cncc(c1)c1ncc(cn1)C(=O)N[C@@H]1COCC1
Isomeric SMILES CCOc1cccnc1Oc1cncc(c1)c1ncc(cn1)C(=O)N[C@H]1CCOC1
InChI InChI=1S/C21H21N5O4/c1-2-29-18-4-3-6-23-21(18)30-17-8-14(9-22-12-17)19-24-10-15(11-25-19)20(27)26-16-5-7-28-13-16/h3-4,6,8-12,16H,2,5,7,13H2,1H3,(H,26,27)/t16-/m0/s1
InChI Key UKBQFBRPXKGJPY-INIZCTEOSA-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/)
Bioactivity Comments
Ervogastat has vanishingly low potency (IC50 >50 μM) at monoacylglycerol O-acyltransferases 1-3 (MOGAT1-3) and diacylglycerol O-acyltransferase 1 (DGAT1).
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
diacylglycerol O-acyltransferase 2 Hs Inhibitor Inhibition 7.8 pIC50 - 2
⤷ pIC50 7.8 (IC50 1.72x10-8 M) [2]
diacylglycerol O-acyltransferase 2 Rn Inhibitor Inhibition 6.1 pIC50 - 2
⤷ pIC50 6.1 (IC50 8.33x10-7 M) [2]
Targets where the ligand is described in the comment field
Target Comment
diacylglycerol O-acyltransferase 2 DGAT2 is expressed in liver and adipose tissues where its substrate is exclusively diacylglycerol (DAG). Gene knock-out of Dgat2 in rodent models is lethal (in the early post-natal period), but inhibition of hepatic DGAT2 in adult animals induces an improved plasma lipoprotein profile that is translatable to therapeutic benefit in metabolic disease. Based in this latter discovery, DGAT2 is an active pharmacological target for the treatment of metabolic diseases such as non-alcoholic steatohepatitis. Inhibitors like ervogastat are predicted to reduce accumulation of fibrosis-inducing triglycerides in the liver. The enzyme has also been implicated in amyloid-β induced lipid droplet-mediated microglial dysfunction and neuronal damage in Alzheimer's disease model mice [3].