CPI-1205   Click here for help

GtoPdb Ligand ID: 9115

Synonyms: compound 13 [PMID: 27739677] | CPI 1205 | CPI1205
Compound class: Synthetic organic
Comment: CPI-1205 is an orally available selective inhibitor of the histone lysine methyltransferase EZH2, with potential antineoplastic activity [4]. The developer is Constellation Pharmaceuticals whose patents WO2012068589 [2] and more recently, WO2014151142A1 [1], claim many compounds for their potential to modulate methylation modifying enzymes. WO2014151142A1 specifically claims inhibition of EZH2, with in vitro IC50 values vs. EZH2 for compounds 100-145 presented in Table 2. See also Garapaty-Ra et al. (2013) [3] for further examples of EZH2/EZH1 inhibitors developed by Constellation Pharmaceuticals.
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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 4
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 79.36
Molecular weight 518.25
XLogP 5.68
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 COc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n(c2c1cccc2)C(C1CCN(CC1)CC(F)(F)F)C
Isomeric SMILES COc1cc(C)[nH]c(=O)c1CNC(=O)c1c(C)n(c2c1cccc2)[C@@H](C1CCN(CC1)CC(F)(F)F)C
InChI InChI=1S/C27H33F3N4O3/c1-16-13-23(37-4)21(25(35)32-16)14-31-26(36)24-18(3)34(22-8-6-5-7-20(22)24)17(2)19-9-11-33(12-10-19)15-27(28,29)30/h5-8,13,17,19H,9-12,14-15H2,1-4H3,(H,31,36)(H,32,35)/t17-/m1/s1
InChI Key HPODOLXTMDHLLC-QGZVFWFLSA-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. Albrecht BK, Audia JE, Cook A, Cote A, Dakin LA, Gehling VS, Harmange J-C, Nasvenschuk CG, Vaswani RG. (2014)
Modulators of methyl modifying enzymes, compositions and uses thereof.
Patent number: WO2014151142 A1. Assignee: Constellation Pharmaceuticals, Inc.. Priority date: 15/03/2013. Publication date: 25/09/2014.
2. Albrecht BK, Audia JE, Gagnon A, Harmange J-C, Nasveschuk CG. (2012)
Modulators of methyl modifying enzymes, compositions and uses thereof.
Patent number: WO2012068589 A2. Assignee: Constellation Pharmaceuticals. Priority date: 19/11/2010. Publication date: 24/05/2012.
3. Garapaty-Rao S, Nasveschuk C, Gagnon A, Chan EY, Sandy P, Busby J, Balasubramanian S, Campbell R, Zhao F, Bergeron L et al.. (2013)
Identification of EZH2 and EZH1 small molecule inhibitors with selective impact on diffuse large B cell lymphoma cell growth.
Chem Biol, 20 (11): 1329-39. [PMID:24183969]
4. Vaswani RG, Gehling VS, Dakin LA, Cook AS, Nasveschuk CG, Duplessis M, Iyer P, Balasubramanian S, Zhao F, Good AC et al.. (2016)
Identification of (R)-N-((4-Methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide (CPI-1205), a Potent and Selective Inhibitor of Histone Methyltransferase EZH2, Suitable for Phase I Clinical Trials for B-Cell Lymphomas.
J Med Chem, 59 (21): 9928-9941. [PMID:27739677]