tazemetostat   Click here for help

GtoPdb Ligand ID: 7011

Synonyms: E-7438 | EPZ 6438 | EPZ-6438 | EPZ6438 | Tazverik®
Approved drug
tazemetostat is an approved drug (FDA (2020))
Compound class: Synthetic organic
Comment: Tazemetostat is an oral, potent, first-in-class inhibitor of the histone methyltransferase, enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) that was developed by Epizyme as anovel drug for the treatment of solid tumours and lymphomas with speciific genetic alterations. Link to Epizyme's tazemetostat webpage here.
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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 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.

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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 10
Topological polar surface area 86.9
Molecular weight 572.34
XLogP 5.61
No. Lipinski's rules broken 1
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.

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Canonical SMILES CCN(c1cc(cc(c1C)C(=O)NCc1c(C)cc([nH]c1=O)C)c1ccc(cc1)CN1CCOCC1)C1CCOCC1
Isomeric SMILES CCN(c1cc(cc(c1C)C(=O)NCc1c(C)cc([nH]c1=O)C)c1ccc(cc1)CN1CCOCC1)C1CCOCC1
InChI InChI=1S/C34H44N4O4/c1-5-38(29-10-14-41-15-11-29)32-20-28(27-8-6-26(7-9-27)22-37-12-16-42-17-13-37)19-30(25(32)4)33(39)35-21-31-23(2)18-24(3)36-34(31)40/h6-9,18-20,29H,5,10-17,21-22H2,1-4H3,(H,35,39)(H,36,40)
InChI Key NSQSAUGJQHDYNO-UHFFFAOYSA-N
No information available.
Summary of Clinical Use Click here for help
Tazemetostat is being evaluated in clinical trials for its potential to treat advanced solid tumours (with certain molecularly defined genetic alterations; e.g. INI1 (SMARCB1)-negative tumours [1,3] or those with EZH2 gain-of-function mutations) and B-cell lymphomas (with and without EZH2 mutations). Click here to link to ClinicalTrials.gov's full list of tazemetostat studies.
In July 2019 the FDA accepted Epizyme's New Drug Application (NDA) for accelerated approval of tazemetostat, for the treatment of metastatic or locally advanced epithelioid sarcoma that is ineligible for curative surgery. Following FDA priority review of this NDA Tazemetostat was granted full FDA approval in January 2020, as a treatment for metastatic or locally advanced epithelioid sarcoma (ES) that is not eligble for complete resection. This approval was based on observation of clinically significant and durable responses, and favourable tolerability in the ES cohort of trial NCT02601950. In the EU, tazemetostat is permitted as a treatment for malignant mesothelioma, follicular lymphoma and diffuse large B-cell lymphoma under orphan designations (granted in 2018 by the EMA).