EPZ015666   Click here for help

GtoPdb Ligand ID: 8287

Synonyms: EPZ 015666 | EPZ-015666
PDB Ligand
Compound class: Synthetic organic
Comment: EPZ015666 is a first-in-class, potent, selective and orally bioavailable PRMT5 inhibitor. The pharmaceutical composition may comprise the hydrochloride salt. EPZ015666 is compound 166 in patent WO2014100719 [5].
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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

EPZ015666 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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Click here for structure editor
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 8
Hydrogen bond donors 3
Rotatable bonds 8
Topological polar surface area 99.61
Molecular weight 383.2
XLogP -0.03
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(CN1CCc2c(C1)cccc2)CNC(=O)c1ncnc(c1)NC1COC1
Isomeric SMILES O[C@H](CN1CCc2c(C1)cccc2)CNC(=O)c1ncnc(c1)NC1COC1
InChI InChI=1S/C20H25N5O3/c26-17(10-25-6-5-14-3-1-2-4-15(14)9-25)8-21-20(27)18-7-19(23-13-22-18)24-16-11-28-12-16/h1-4,7,13,16-17,26H,5-6,8-12H2,(H,21,27)(H,22,23,24)/t17-/m0/s1
InChI Key ZKXZLIFRWWKZRY-KRWDZBQOSA-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. Alinari L, Mahasenan KV, Yan F, Karkhanis V, Chung JH, Smith EM, Quinion C, Smith PL, Kim L, Patton JT et al.. (2015)
Selective inhibition of protein arginine methyltransferase 5 blocks initiation and maintenance of B-cell transformation.
Blood, 125 (16): 2530-43. [PMID:25742700]
2. Branscombe TL, Frankel A, Lee JH, Cook JR, Yang Z, Pestka S, Clarke S. (2001)
PRMT5 (Janus kinase-binding protein 1) catalyzes the formation of symmetric dimethylarginine residues in proteins.
J Biol Chem, 276 (35): 32971-6. [PMID:11413150]
3. Chung J, Karkhanis V, Tae S, Yan F, Smith P, Ayers LW, Agostinelli C, Pileri S, Denis GV, Baiocchi RA et al.. (2013)
Protein arginine methyltransferase 5 (PRMT5) inhibition induces lymphoma cell death through reactivation of the retinoblastoma tumor suppressor pathway and polycomb repressor complex 2 (PRC2) silencing.
J Biol Chem, 288 (49): 35534-47. [PMID:24189068]
4. Copeland RA. (2013)
Molecular pathways: protein methyltransferases in cancer.
Clin Cancer Res, 19 (23): 6344-50. [PMID:23958745]
5. Duncan KW, Chesworth R, Boriack-Sjodin PA, Munchhof MJ, Jin L. (2014)
Prmt5 inhibitors and uses thereof.
Patent number: WO2014100719. Assignee: Epizyme, Inc.. Priority date: 21/12/2012. Publication date: 26/06/2014.
6. Li Y, Chitnis N, Nakagawa H, Kita Y, Natsugoe S, Yang Y, Li Z, Wasik M, Klein-Szanto AJ, Rustgi AK et al.. (2015)
PRMT5 Is Required for Lymphomagenesis Triggered by Multiple Oncogenic Drivers.
Cancer Discov, 5 (3): 288-303. [PMID:25582697]
7. Pal S, Baiocchi RA, Byrd JC, Grever MR, Jacob ST, Sif S. (2007)
Low levels of miR-92b/96 induce PRMT5 translation and H3R8/H4R3 methylation in mantle cell lymphoma.
EMBO J, 26 (15): 3558-69. [PMID:17627275]
8. Park JH, Szemes M, Vieira GC, Melegh Z, Malik S, Heesom KJ, Von Wallwitz-Freitas L, Greenhough A, Brown KW, Zheng YG et al.. (2015)
Protein arginine methyltransferase 5 is a key regulator of the MYCN oncoprotein in neuroblastoma cells.
Mol Oncol, 9 (3): 617-27. [PMID:25475372]
9. Stopa N, Krebs JE, Shechter D. (2015)
The PRMT5 arginine methyltransferase: many roles in development, cancer and beyond.
Cell Mol Life Sci, 72 (11): 2041-59. [PMID:25662273]
10. Yang F, Wang J, Ren HY, Jin J, Wang AL, Sun LL, Diao KX, Wang EH, Mi XY. (2015)
Proliferative role of TRAF4 in breast cancer by upregulating PRMT5 nuclear expression.
Tumour Biol, 36 (8): 5901-11. [PMID:25704480]