MAK683   Click here for help

GtoPdb Ligand ID: 10515

Synonyms: EED inhibitor-1 | example 2 [WO2016103155A1] | MAK-683
PDB Ligand
Compound class: Synthetic organic
Comment: MAK683 is an allosteric inhibitor of the protein-protein interaction (PPI) between embryonic ectoderm development protein (EED) and polycomb repressive complex 2 (PRC2; EZH2) that was developped by Novartis for potential antineoplastic activity. It is one of the chemical structures claimed in Novartis' patent WO2016103155A1, and it targets EED [1]. EED has no intrinsic enzymatic activity but it is essential for PRC2 function. EED binds to histone H3K27 trimethylation marks which localizes the PRC2 complex to the chromatin substrate and allosterically activates PRC2's methyltransferase activity. Disruption of the EED-EZH2 PPI results in a loss of H3K27me3-stimulated PRC2 activity and reduces histone H3K27 trimethylation. In EZH2-mutated and PRC2-dependent cancer cells this PPI disruption modifies gene expression patterns within cancer pathways and ultimately decreases tumour cell proliferation.
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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 5
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 77.23
Molecular weight 376.14
XLogP 5.13
No. Lipinski's rules broken 1

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 Fc1ccc2c(c1CNc1ncc(c3n1cnn3)c1cccnc1C)CCO2
Isomeric SMILES Fc1ccc2c(c1CNc1ncc(c3n1cnn3)c1cccnc1C)CCO2
InChI InChI=1S/C20H17FN6O/c1-12-13(3-2-7-22-12)16-10-24-20(27-11-25-26-19(16)27)23-9-15-14-6-8-28-18(14)5-4-17(15)21/h2-5,7,10-11H,6,8-9H2,1H3,(H,23,24)
InChI Key XLIBABIFOBYHSV-UHFFFAOYSA-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/)
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methylpyridin-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine
Synonyms Click here for help
EED inhibitor-1 | example 2 [WO2016103155A1] | MAK-683
Database Links Click here for help
BindingDB Ligand 291687
CAS Registry No. 1951408-58-4 (source: PubChem)
GtoPdb PubChem SID 387065597
PubChem CID 121412508
RCSB PDB Ligand EJR
Search Google for chemical match using the InChIKey XLIBABIFOBYHSV-UHFFFAOYSA-N
Search Google for chemicals with the same backbone XLIBABIFOBYHSV
UniChem Compound Search for chemical match using the InChIKey XLIBABIFOBYHSV-UHFFFAOYSA-N
UniChem Connectivity Search for chemical match using the InChIKey XLIBABIFOBYHSV-UHFFFAOYSA-N

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MedChemExpress
MAK683 (links to external site)
Cat. No. HY-103663