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Tazemetostat

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Also known as E-7438E7438EPZ-6438EPZ6438EPZ 6438TAZEMETOSTAT (EPZ-6438)TazmetostatTazemelostat

Summary

Tazemetostat (CHEMBL3414621) is an approved small molecule (ATC L01XX72) targeting EZH2; indicated across 13 conditions including neoplasm and sarcoma; with CIViC clinical evidence for 20 variant-indication associations (e.g. EZH2 Activating Mutation in follicular lymphoma).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: L01XX72
  • Targets: 1 (EZH2)
  • Indications: 13 conditions
  • Clinical trials: 53
  • Precision-oncology evidence (CIViC): 20 variant–indication associations
  • Chemistry: 572.7 Da · C34H44N4O4

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL3414621
NameTazemetostat
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID66558664
ATCL01XX72
Molecular formulaC34H44N4O4
Molecular weight572.7
InChIKeyNSQSAUGJQHDYNO-UHFFFAOYSA-N

SMILES: CCN(C1CCOCC1)C2=CC(=CC(=C2C)C(=O)NCC3=C(C=C(NC3=O)C)C)C4=CC=C(C=C4)CN5CCOCC5

IUPAC name: N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-[ethyl(oxan-4-yl)amino]-2-methyl-5-[4-(morpholin-4-ylmethyl)phenyl]benzamide

Also known as: E-7438, E7438, EPZ-6438, EPZ6438, Tazemetostat, EPZ 6438, TAZEMETOSTAT, TAZEMETOSTAT (EPZ-6438), Tazmetostat, tazemetostat, Tazemetostat (EPZ-6438), Tazemelostat

Parent form; salt/anhydrous children: CHEMBL4594260

Patent coverage: 762 distinct patent families (1,869 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 1,467 (78%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
EZH2enhancer of zeste 2 polycomb repressive complex 2 subunitInhibition7.966.9%Q15910

Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: Histone-lysine N-methyltransferase EZH2, Histone-lysine N-methyltransferase EZH1, Polycomb protein EED, Voltage-gated inwardly rectifying potassium channel KCNH2, cGMP-inhibited 3’,5’-cyclic phosphodiesterase 3A, 3’,5’-cyclic-AMP phosphodiesterase 4D, EZH1/SUZ12/EED/AEBP2/RBBP4 complex, Nuclear receptor subfamily 1 group I member 2, Prostaglandin G/H synthase 1, Bile salt export pump.

Bioactivity

ChEMBL activities: 60 potent at pChembl ≥ 5 of 66 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
EZH29.47IC500.34nMCHEMBL_ACT_20702134
EZH29IC501nMCHEMBL_ACT_15675844
EZH29IC501nMCHEMBL_ACT_15675866
EZH28.92IC501.2nMCHEMBL_ACT_25993459
EZH28.92IC501.2nMCHEMBL_ACT_26192422
EZH28.85IC501.43nMCHEMBL_ACT_26197448
EZH28.8IC501.6nMCHEMBL_ACT_26035447
EZH28.77IC501.7nMCHEMBL_ACT_26192492
EZH28.72IC501.9nMCHEMBL_ACT_26192456
EED8.7IC502nMCHEMBL_ACT_18034228
EZH28.66IC502.2nMCHEMBL_ACT_26192545
EZH28.61IC502.45nMCHEMBL_ACT_28881044
EZH28.6Ki2.5nMCHEMBL_ACT_15210936
EZH28.6Ki2.5nMCHEMBL_ACT_24994612
EZH28.6Ki2.5nMCHEMBL_ACT_25500519
EZH28.6IC502.5nMCHEMBL_ACT_26192547
EZH28.57IC502.67nMCHEMBL_ACT_25529479
EHMT28.54IC502.9nMCHEMBL_ACT_29119553
EZH28.5IC503.19nMCHEMBL_ACT_17610891
EZH28.43IC503.7nMCHEMBL_ACT_24382648
EED8.4IC504nMCHEMBL_ACT_18377188
EZH28.4IC504nMCHEMBL_ACT_24707226
EZH28.4IC504nMCHEMBL_ACT_25500518
EZH28.37IC504.3nMCHEMBL_ACT_26192543
EZH28.3EC505nMCHEMBL_ACT_23263820
EZH28.22EC506nMCHEMBL_ACT_23263818
EZH28.15IC507.03nMCHEMBL_ACT_26197461
EZH28.04Kd9.13nMCHEMBL_ACT_25889210
EZH27.96IC5011.07nMCHEMBL_ACT_17697107
EZH27.96IC5011.07nMCHEMBL_ACT_17776715

Target pathways

Aggregated over 1 target gene(s): EZH2.

Top Reactome pathways

10 total, by targets touching each:

PathwayTargetsGenes
PRC2 methylates histones and DNA1EZH2
Oxidative Stress Induced Senescence1EZH2
PKMTs methylate histone lysines1EZH2
Activation of anterior HOX genes in hindbrain development during early embryogenesis1EZH2
Regulation of PTEN gene transcription1EZH2
Transcriptional Regulation by E2F61EZH2
HCMV Early Events1EZH2
Defective pyroptosis1EZH2
Negative Regulation of CDH1 Gene Transcription1EZH2
Regulation of PD-L1(CD274) transcription1EZH2

Dominant GO biological processes

GO termTargets
G1/S transition of mitotic cell cycle1
negative regulation of transcription by RNA polymerase II1
chromatin organization1
DNA methylation-dependent constitutive heterochromatin formation1
regulation of DNA-templated transcription1
positive regulation of cell population proliferation1
positive regulation of epithelial to mesenchymal transition1
regulation of gliogenesis1
skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration1
cardiac muscle hypertrophy in response to stress1
cerebellar cortex development1
hippocampus development1
B cell differentiation1
keratinocyte differentiation1
positive regulation of cell migration1

Indications & clinical

Indications

13 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
neoplasm4MONDO:0005070EFO:0000616
neoplasm of mature B-cells3MONDO:0004949EFO:0000096
sarcoma3MONDO:0005089MONDO:0017387
follicular lymphoma3MONDO:0018906MONDO:0018906
lymphoma2MONDO:0005062EFO:0000574
mesothelioma2MONDO:0005065EFO:0000588
diffuse large B-cell lymphoma1MONDO:0018905EFO:0000403
metastatic prostate carcinoma1MONDO:0004956EFO:0000196
urothelial carcinoma1MONDO:0040679EFO:0008528
head and neck squamous cell carcinoma1MONDO:0010150EFO:0000181
plasma cell myeloma1MONDO:0009693EFO:0001378
non-small cell lung carcinoma1MONDO:0005233EFO:0003060
acute myeloid leukemia1MONDO:0018874EFO:0000222

Clinical trials

Total trials: 53.

Phase distribution

PhaseTrials
PHASE219
PHASE117
PHASE1/PHASE213
Not specified3
PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT04224493PHASE3ACTIVE_NOT_RECRUITINGA Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus Placebo in Combination With Lenalidomide Plus Rituximab in Adult Patients at Least 18 Years of Age With Relapsed/Refractory Follicular Lymphoma.
NCT02889523PHASE1/PHASE2ACTIVE_NOT_RECRUITINGStudy of Tazemetostat in Newly Diagnosed Diffuse Large B Cell and Follicular Lymphoma Patients Treated by Chemiotherapy
NCT03155620PHASE2ACTIVE_NOT_RECRUITINGTargeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03348631PHASE2ACTIVE_NOT_RECRUITINGTazemetostat in Treating Patients With Recurrent Ovarian or Endometrial Cancer
NCT03854474PHASE1/PHASE2ACTIVE_NOT_RECRUITINGTesting the Addition of Tazemetostat to the Immunotherapy Drug, Pembrolizumab (MK-3475), in Advanced Urothelial Carcinoma
NCT04917042PHASE2ACTIVE_NOT_RECRUITINGTazemetostat in Malignant Peripheral Nerve Sheath Tumors
NCT05151588PHASE2NOT_YET_RECRUITINGInduction Chemotherapy and Tazemetostat for Locally Advanced SMARCB1-deficient Sinonasal Carcinoma
NCT05372354PHASE1/PHASE2RECRUITINGA Study to Evaluate Safety, Drug Levels and Effectiveness of CC-92480 (BMS-986348) in Combination With Other Treatments in Participants With Relapsed or Refractory Multiple Myeloma
NCT05407441PHASE1/PHASE2ACTIVE_NOT_RECRUITINGTazemetostat+Nivo/Ipi in INI1-Neg/SMARCA4-Def Tumors
NCT05551936PHASE1/PHASE2ACTIVE_NOT_RECRUITINGA Study of Tazemetostat With Rituximab and Abbreviated Bendamustine in the Frontline Treatment of High Tumor Burden Follicular Lymphoma
NCT05890352PHASE2RECRUITINGStudy Adding Drugs to Usual Treatment for Large B-Cell Lymphoma That Returned or Did Not Respond to Treatment
NCT05994235PHASE2ACTIVE_NOT_RECRUITINGTazemetostat and Mosunetuzumab in Untreated Follicular Lymphoma
NCT06242834PHASE2ACTIVE_NOT_RECRUITINGPembrolizumab and Tazemetostat to Overcome Immune Tolerance Following ASCT or CAR T-cell Therapy in Patients With Aggressive B-Cell Non-Hodgkin’s Lymphoma
NCT07209163PHASE1/PHASE2NOT_YET_RECRUITINGCombination Therapy With Tazemetostat in Relapsed and Refractory Peripheral T-cell Lymphoma
NCT07407283PHASE1/PHASE2RECRUITINGA Clinical Study of SHR-4394 in Combination With Anti-tumor Therapy in Prostate Cancer
NCT01897571PHASE1/PHASE2COMPLETEDStudy of Tazemetostat as Single Agent in Solid Tumors or B-cell Lymphomas and in Combination With Prednisolone in DLBCL
NCT02601950PHASE2COMPLETEDA Study of Tazemetostat in Adult Participants With Soft Tissue Sarcoma
NCT02860286PHASE2COMPLETEDStudy of the EZH2 Inhibitor Tazemetostat in Malignant Mesothelioma
NCT02875548PHASE1/PHASE2COMPLETEDA Study to Assess Long-term Safety of Tazemetostat in Adult Participants of All Ages With Any Disease Treated With Tazemetostat in a Previous Clinical Study
NCT03213665PHASE2COMPLETEDTazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03456726PHASE2COMPLETEDStudy of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin’s Lymphoma With EZH2 Gene Mutation
NCT04179864PHASE1/PHASE2TERMINATEDA Study of Tazemetostat With Enzalutamide or Abiraterone/Prednisone in Participants With Advanced Prostate Cancer
NCT04705818PHASE2COMPLETEDCombining Epigenetic And Immune Therapy to Beat Cancer.
NCT04762160PHASE2TERMINATEDSYMPHONY-2, A Trial to Examine Combination of Tazemetostat With Rituximab in Subjects With Relapsed/Refractory Follicular Lymphoma
NCT05018975PHASE2WITHDRAWNTazemetostat for the Treatment of Moderate to Severe COVID-19 Infection
NCT05023655PHASE2TERMINATEDPhase II Study of Tazemetostat in Solid Tumors Harboring an ARID1A Mutation
NCT05152459PHASE1/PHASE2WITHDRAWNTazemetostat in Combination With Umbralisib and Ublituximab for the Treatment Relapsed or Refractory Follicular Lymphoma
NCT05205252PHASE1/PHASE2WITHDRAWNA Study of Tazemetostat in Combination With Various Treatments in Participants With Blood Cancer.
NCT05467943PHASE2COMPLETEDTazemetostat for the Treatment of Relapsed/Refractory Follicular Lymphoma
NCT05604417PHASE1/PHASE2WITHDRAWNZandelisib + Tazemetostat in R/R Follicular Lymphoma
NCT05713110PHASE2COMPLETEDA Study of Tazemetostat in Combination With HMPL-689 in Patients With Relapsed/Refractory Lymphoma
NCT06575686PHASE2SUSPENDEDEpcoritamab and Tazemetostat for the Treatment of Relapsed or Refractory Grade I-IIIa Follicular Lymphoma
NCT06692452PHASE2WITHDRAWNTazemetostat Plus CHOP in 1L T-cell Lymphoma
NCT04846478PHASE1ACTIVE_NOT_RECRUITINGPhase Ia/Ib Talazoparib + Tazemetostat for mCRPC
NCT05627232PHASE1RECRUITINGTazemetostat and Palbociclib With CPX-351for R/R AML
NCT05627245PHASE1ACTIVE_NOT_RECRUITINGTesting the Safety of the Anti-cancer Drugs Tazemetostat and Belinostat in Patients With Lymphomas That Have Resisted Treatment
NCT05934838PHASE1RECRUITINGA Feasibility Trial of Tazemetostat Plus CAR T Cell Therapy in B-cell Lymphomas
NCT02220842PHASE1COMPLETEDA Safety and Pharmacology Study of Atezolizumab (MPDL3280A) Administered With Obinutuzumab or Tazemetostat in Participants With Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-cell Lymphoma
NCT02601937PHASE1COMPLETEDEZH2 Inhibitor Tazemetostat in Pediatric Subjects With Relapsed or Refractory INI1-Negative Tumors or Synovial Sarcoma
NCT03009344PHASE1COMPLETEDA Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin’s Lymphoma

Clinical evidence (CIViC)

Variant × indication × effect (20 predictive associations from 23 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
EZH2 Activating MutationFollicular LymphomaSensitivity/ResponseTazemetostatCIViC AEID9709 +1
EZH2 Y646S OR EZH2 Y646F OR EZH2 Y646H OR EZH2 Y646C OR EZH2 Y646N OR EZH2 A692V OR EZH2 A682GB-cell Non-Hodgkin LymphomaSensitivity/ResponseTazemetostatCIViC AEID11220
SMARCB1 DeletionEpithelioid SarcomaSensitivity/ResponseTazemetostatCIViC AEID9992
EZH2 Mutation OR SMARCA4 Loss OR SMARCB1 LossCancerSensitivity/ResponseTazemetostatCIViC BEID11694
EZH2 Y646NDiffuse Large B-cell LymphomaSensitivity/ResponseTazemetostat + AtezolizumabCIViC BEID11112
EZH2 Y646S OR EZH2 Y646F OR EZH2 Y646H OR EZH2 Y646C OR EZH2 Y646N OR EZH2 A692V OR EZH2 A682GFollicular LymphomaSensitivity/ResponseTazemetostatCIViC BEID11109
EZH2 Y646S OR EZH2 Y646F OR EZH2 Y646H OR EZH2 Y646C OR EZH2 Y646N OR EZH2 A692V OR EZH2 A682GDiffuse Large B-cell LymphomaSensitivity/ResponseTazemetostatCIViC BEID11110
SMARCB1 LossAtypical Teratoid Rhabdoid TumorSensitivity/ResponseTazemetostatCIViC BEID11180
SMARCB1 LossPoorly Differentiated ChordomaSensitivity/ResponseTazemetostatCIViC CEID11178 +1
EZH2 Y646HDiffuse Large B-cell LymphomaSensitivity/ResponseTazemetostatCIViC CEID9377
EZH2 expressionDiffuse Large B-cell Lymphoma Germinal Center B-cell TypeSensitivity/ResponseTazemetostatCIViC CEID11108
SMARCA4 UnderexpressionCancerSensitivity/ResponseTazemetostatCIViC CEID6373
SMARCB1 LossEpithelioid SarcomaSensitivity/ResponseTazemetostatCIViC CEID11181
EZH2 Y646FNon-Hodgkin LymphomaSensitivity/ResponseTazemetostatCIViC DEID11000 +1
EZH2 A682GFollicular LymphomaSensitivity/ResponseTazemetostatCIViC DEID12877
EZH2 OverexpressionNeuroblastomaSensitivity/ResponseTazemetostat + GSK126CIViC DEID9115
EZH2 Y646FB-cell LymphomaSensitivity/ResponseTazemetostatCIViC DEID10999
EZH2 Y646NDiffuse Large B-cell LymphomaSensitivity/ResponseTazemetostatCIViC DEID11049
SMARCB1 DeletionRhabdoid CancerSensitivity/ResponseTazemetostatCIViC DEID1740
SMARCB1 UnderexpressionSynovial SarcomaSensitivity/ResponseTazemetostatCIViC DEID1739

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

3 molecules share ≥1 primary target. Top 3 by shared-target count:

MoleculeSourceStatusShared targets
MEVROMETOSTATChEMBLPhase 2EZH2
VALEMETOSTATChEMBLPhase 2EZH2
ZEPRUMETOSTATChEMBLPhase 2EZH2

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot