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Entinostat

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Also known as SNDX-275SID29217590SID529250SID137275820MS-275EntinostatÊEntinostatÂ

Summary

Entinostat (CHEMBL27759) is a phase-3 clinical-stage small-molecule EC 3.5.1.98 (histone deacetylase) inhibitor (ATC L01XH05) targeting HDAC2, HDAC3, and HDAC9; indicated across 37 conditions including breast carcinoma and breast neoplasm.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • ATC class: L01XH05
  • Targets: 4 (HDAC2, HDAC3, HDAC9…)
  • Indications: 37 conditions
  • Clinical trials: 73
  • Chemistry: 376.4 Da · C21H20N4O3

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL27759
NameEntinostat
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID4261
ChEBICHEBI:132082
ATCL01XH05
Molecular formulaC21H20N4O3
Molecular weight376.4
InChIKeyINVTYAOGFAGBOE-UHFFFAOYSA-N

SMILES: C1=CC=C(C(=C1)N)NC(=O)C2=CC=C(C=C2)CNC(=O)OCC3=CN=CC=C3

IUPAC name: pyridin-3-ylmethyl N-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]carbamate

ChEBI definition: A member of the class of benzamides resulting from the formal condensation of the carboxy group of the pyridin-3-ylmethyl carbamate derivative of p-(aminomethyl)benzoic acid with one of the amino groups of benzene-1,2-diamine. It is an inhibitor of histone deacetylase isoform 1 (HDAC1) and isoform 3 (HDAC3).

Pharmacological roles (ChEBI): EC 3.5.1.98 (histone deacetylase) inhibitor, antineoplastic agent, apoptosis inducer.

Also known as: Entinostat, SNDX-275, entinostat, SID29217590, SID529250, ENTINOSTAT, SID137275820, MS-275, EntinostatÊ, EntinostatÂ

Parent form; salt/anhydrous children: CHEMBL3093129

Patent coverage: 2,550 distinct patent families (6,584 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 6,516 (99%) 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
HDAC2histone deacetylase 2Inhibition5.943.1%Q92769
HDAC3histone deacetylase 3Inhibition5.6495.1% (common-essential)O15379
HDAC9histone deacetylase 9Inhibition6.30%Q9UKV0
HDAC1histone deacetylase 1Inhibition6.744.5%Q13547

Broader ChEMBL bioactivity targets: 17 (assay-derived). Sample: Histone deacetylase 3, Protein deacetylase HDAC6, Histone deacetylase 2, Histone deacetylase, Histone deacetylase 3/Nuclear receptor corepressor 2 (HDAC3/NCoR2), Histone deacetylase (HDAC1 and HDAC2), Histone deacetylase 5, Histone deacetylase 7, Histone deacetylase 8, Histone deacetylase 1.

Bioactivity

ChEMBL activities: 248 potent at pChembl ≥ 5 of 262 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
HDAC19.7IC500.2nMCHEMBL_ACT_22974856
HDAC99.3IC500.5nMCHEMBL_ACT_22974862
HDAC28.92IC501.2nMCHEMBL_ACT_22974857
HDAC38.64IC502.3nMCHEMBL_ACT_22974858
HDAC28.24Ki5.7nMCHEMBL_ACT_25724144
HDAC28.22Ki6nMCHEMBL_ACT_24778307
HDAC17.85IC5014nMCHEMBL_ACT_28736108
HDAC27.82IC5015nMCHEMBL_ACT_3329000
HDAC17.66Ki22nMCHEMBL_ACT_3389976
HDAC37.62Ki24nMCHEMBL_ACT_24778385
HDAC17.6IC5025nMCHEMBL_ACT_3328999
HDAC37.57Ki27nMCHEMBL_ACT_24778334
HDAC67.47IC5034nMCHEMBL_ACT_24804881
HDAC37.46IC5035nMCHEMBL_ACT_25676905
HDAC37.41Ki39nMCHEMBL_ACT_24778304
HDAC17.36IC5044nMCHEMBL_ACT_3596976
HDAC17.27IC5053.89nMCHEMBL_ACT_19014037
HDAC27.19Ki65nMCHEMBL_ACT_3389977
HDAC37.15IC5071nMCHEMBL_ACT_25676903
HDAC27.14Ki73nMCHEMBL_ACT_24778335
HDAC37.11IC5077.18nMCHEMBL_ACT_19014035
HDAC17.08IC5083nMCHEMBL_ACT_25676868
HDAC17.03IC5093nMCHEMBL_ACT_25057111
HDAC17IC5099nMCHEMBL_ACT_18095222
HDAC26.97IC50108.2nMCHEMBL_ACT_19014036
HDAC16.96IC50110nMCHEMBL_ACT_1792274
HDAC16.93IC50118nMCHEMBL_ACT_19142744
HDAC16.92IC50120nMCHEMBL_ACT_2118124
HDAC16.92IC50120nMCHEMBL_ACT_2161826
HDAC16.92IC50120nMCHEMBL_ACT_2623809

Target pathways

Aggregated over 4 target gene(s): HDAC2, HDAC3, HDAC9, HDAC1.

Top Reactome pathways

58 total, by targets touching each:

PathwayTargetsGenes
NOTCH1 Intracellular Domain Regulates Transcription4HDAC1, HDAC2, HDAC3, HDAC9
Constitutive Signaling by NOTCH1 PEST Domain Mutants4HDAC1, HDAC2, HDAC3, HDAC9
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants4HDAC1, HDAC2, HDAC3, HDAC9
Notch-HLH transcription pathway4HDAC1, HDAC2, HDAC3, HDAC9
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)4HDAC1, HDAC2, HDAC3, HDAC9
p75NTR negatively regulates cell cycle via SC13HDAC1, HDAC2, HDAC3
HDACs deacetylate histones3HDAC1, HDAC2, HDAC3
Regulation of PTEN gene transcription3HDAC1, HDAC2, HDAC3
Regulation of MECP2 expression and activity3HDAC1, HDAC2, HDAC3
STAT3 nuclear events downstream of ALK signaling3HDAC1, HDAC2, HDAC3
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression2HDAC1, HDAC2
NoRC negatively regulates rRNA expression2HDAC1, HDAC2
SUMOylation of chromatin organization proteins2HDAC1, HDAC2
Regulation of TP53 Activity through Acetylation2HDAC1, HDAC2
RNA Polymerase I Transcription Initiation2HDAC1, HDAC2
MECP2 regulates neuronal receptors and channels2HDAC1, HDAC2
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes2HDAC1, HDAC2
Potential therapeutics for SARS2HDAC1, HDAC2
Negative Regulation of CDH1 Gene Transcription2HDAC1, HDAC2
Factors involved in megakaryocyte development and platelet production2HDAC1, HDAC2
Regulation of endogenous retroelements by KRAB-ZFP proteins2HDAC1, HDAC2
Transcriptional regulation of brown and beige adipocyte differentiation by EBF22HDAC1, HDAC2
Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)2HDAC1, HDAC2
NuRD complex assembly2HDAC1, HDAC2
Interaction of NuRD complexes with transcription factors2HDAC1, HDAC2
Transcription of E2F targets under negative control by DREAM complex1HDAC1
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC11HDAC1
G0 and Early G11HDAC1
PPARA activates gene expression1HDAC3
Formation of the beta-catenin:TCF transactivating complex1HDAC1

Dominant GO biological processes

GO termTargets
negative regulation of transcription by RNA polymerase II4
negative regulation of DNA-templated transcription4
chromatin organization4
circadian regulation of gene expression3
negative regulation of apoptotic process3
positive regulation of transcription by RNA polymerase II3
rhythmic process3
chromatin remodeling2
positive regulation of cell population proliferation2
response to xenobiotic stimulus2
epidermal cell differentiation2
negative regulation of cell migration2
negative regulation of transforming growth factor beta receptor signaling pathway2
heterochromatin formation2
positive regulation of intracellular estrogen receptor signaling pathway2

Indications & clinical

Indications

37 indications (0 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
breast carcinoma3MONDO:0004989EFO:0000305
breast neoplasm3MONDO:0021100EFO:0003869
neoplasm3MONDO:0005070EFO:0000616
Hodgkins lymphoma2MONDO:0004952EFO:0000183
myelodysplastic syndrome2MONDO:0018881EFO:0000198
acute myeloid leukemia2MONDO:0018874EFO:0000222
clear cell renal carcinoma2MONDO:0005005EFO:0000349
lymphoma2MONDO:0005062EFO:0000574
renal cell carcinoma2MONDO:0005086EFO:0000681
melanoma2MONDO:0005105EFO:0000756
non-small cell lung carcinoma2MONDO:0005233EFO:0003060
triple-negative breast carcinoma2MONDO:0005494EFO:0005537
male breast carcinoma2MONDO:0005628EFO:0006861
rectal cancer2MONDO:0006519EFO:1000657
neuroendocrine neoplasm2MONDO:0019496EFO:1001901
colonic neoplasm2MONDO:0005401MONDO:0021063
uveal melanoma2MONDO:0006486EFO:1000616
central nervous system cancer1MONDO:0002714EFO:0000326
prostate adenocarcinoma1MONDO:0005082EFO:0000673
exocrine pancreatic carcinoma1MONDO:0005192EFO:0002618
kidney disorder1MONDO:0005240EFO:0003086
peritoneal neoplasm1MONDO:0006901MONDO:0002087
fallopian tube neoplasm1MONDO:0021092MONDO:0002158
kidney cancer1MONDO:0002367MONDO:0002367
ovarian cancer1MONDO:0008170MONDO:0008170
carcinoma of esophagus1MONDO:0019086EFO:0002916
oropharynx cancer1MONDO:0004608EFO:1001931
penile neoplasm1MONDO:0006895MONDO:0001325
vaginal cancer1MONDO:0001402MONDO:0001402
leukemia1MONDO:0005059EFO:0000565
colorectal neoplasm1MONDO:0005335MONDO:0005575
lung neoplasm1MONDO:0021117MONDO:0008903

5 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 73.

Phase distribution

PhaseTrials
PHASE129
PHASE226
PHASE1/PHASE214
PHASE32
EARLY_PHASE12

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02115282PHASE3ACTIVE_NOT_RECRUITINGExemestane With or Without Entinostat in Treating Patients With Recurrent Hormone Receptor-Positive Breast Cancer That is Locally Advanced or Metastatic
NCT03538171PHASE3UNKNOWNPh3 Study of Exemestane With or Without Entinostat in Chinese Patients With Hormone Receptor-Positive, Locally Advanced or Metastatic Breast Cancer
NCT01038778PHASE1/PHASE2ACTIVE_NOT_RECRUITINGEntinostat in Combination With Aldesleukin in Treating Patients With Metastatic Kidney Cancer
NCT03179930PHASE2ACTIVE_NOT_RECRUITINGCombination Therapy With Entinostat and Pembrolizumab in Relapsed and Refractory Lymphomas
NCT03501381PHASE2ACTIVE_NOT_RECRUITINGHigh Dose IL 2 and Entinostat in RCC
NCT03838042PHASE1/PHASE2RECRUITINGINFORM2 Study Uses Nivolumab and Entinostat in Children and Adolescents With High-risk Refractory Malignancies
NCT03978624PHASE2ACTIVE_NOT_RECRUITINGWindow of Opportunity Study of Pembrolizumab Alone and in Combinations in Bladder Cancer
NCT04708470PHASE1/PHASE2ACTIVE_NOT_RECRUITINGA Phase I/II Study of Combination Immunotherapy for Advanced Cancers Including HPV-Associated Malignancies, Small Bowel, and Colon Cancers
NCT05053971PHASE1/PHASE2RECRUITINGTesting A New Anti-cancer Drug Combination, Entinostat and ZEN003694, for Advanced and Refractory Solid Tumors
NCT07235618PHASE2NOT_YET_RECRUITINGA Study of Entinostat in Combination With Fulvestrant for the Treatment of Locally Advanced or Metastatic Breast Cancer
NCT07261592PHASE1/PHASE2NOT_YET_RECRUITINGEntinostat & Chemotherapy for Locally Advanced or Metastatic Bladder Cancer
NCT07330544PHASE2RECRUITINGA Phase II Clinical Study Evaluating Entinostat With or Without Anlotinib + Fulvestrant for the Treatment of Hormone Receptor (HR) -Positive, Human Epidermal Growth Factor Receptor-2 (HER-2) -Negative Advanced Breast Cancer That Relapsed or Progressed After Endocrine Therapy
NCT07441486PHASE2NOT_YET_RECRUITINGA Single-arm, Prospective, Phase II Clinical Study of the Combination of Entinostat and Oral Paclitaxel in the Treatment of HR+HER2- Advanced Breast Cancer
NCT07492394PHASE2RECRUITINGDalpiciclib With or Without Entinostat and Letrozole in HR+/HER2- Early Breast Cancer
NCT00313586PHASE2COMPLETEDAzacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia
NCT00387465PHASE1/PHASE2COMPLETEDAzacitidine and Entinostat in Treating Patients With Recurrent Advanced Non-Small Cell Lung Cancer
NCT00462605PHASE2COMPLETEDMS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia
NCT00602030PHASE1/PHASE2COMPLETEDStudy to Evaluate Erlotinib With or Without SNDX-275 (Entinostat) in the Treatment of Patients With Advanced NSCLC
NCT00676663PHASE2COMPLETEDStudy to Evaluate Exemestane With and Without Entinostat (SNDX-275) in Treatment of Postmenopausal Women With Advanced Breast Cancer
NCT00750698PHASE2TERMINATEDA Phase 2 Exploratory Study of Erlotinib and SNDX-275 in Participants With Non-small Cell Lung Carcinoma Who Are Progressing on Erlotinib
NCT00828854PHASE2COMPLETEDStudy of the Effect of the Addition of SNDX-275 (Entinostat) to Continued Aromatase Inhibitor (AI) Therapy in Postmenopausal Women With ER+ Breast Cancer Whose Disease is Progressing
NCT00866333PHASE2TERMINATEDA Phase 2 Multi-Center Study of Entinostat (SNDX-275) in Patient With Relapsed or Refractory Hodgkin’s Lymphoma
NCT01105377PHASE2COMPLETEDAzacitidine and Entinostat in Treating Patients With Metastatic Colorectal Cancer
NCT01207726PHASE2TERMINATEDAzacitidine and Entinostat in Treating Patients With Stage I Non-Small Cell Lung Cancer That Has Been Removed By Surgery
NCT01234532PHASE2TERMINATEDEntinostat and Anastrozole in Treating Postmenopausal Women With TNBC That Can Be Removed by Surgery
NCT01349959PHASE2COMPLETEDAzacitidine and Entinostat in Treating Patients With Advanced Breast Cancer
NCT01383447PHASE1/PHASE2TERMINATEDEntinostat And Imatinib Mesylate In Treating Patients With Relapsed or Refractory Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
NCT01928576PHASE2COMPLETEDPhase II Anti-PD1 Epigenetic Therapy Study in NSCLC.
NCT01935947PHASE2TERMINATEDAzacitidine and Entinostat Before Chemotherapy in Treating Patients With Advanced Non-small Cell Lung Cancer
NCT02115594PHASE2WITHDRAWNPhase 2 Study of Fulvestrant With and Without Entinostat in Postmenopausal Women With ER+ Advanced Breast Cancer
NCT02437136PHASE1/PHASE2COMPLETEDPh1b/2 Dose-Escalation Study of Entinostat With Pembrolizumab in Non-small Cell Lung Cancer (NSCLC) With Expansion Cohorts in NSCLC, Melanoma, and Colorectal Cancer (CRC)
NCT02697630PHASE2COMPLETEDEfficacy Study of Pembrolizumab With Entinostat to Treat Metastatic Melanoma of the Eye
NCT02708680PHASE1/PHASE2COMPLETEDRandomized Phase 2 Study of Atezolizumab and Entinostat in Patients With aTN Breast Cancer With Phase 1b Lead In
NCT02915523PHASE1/PHASE2COMPLETEDStudy of Avelumab With or Without Entinostat in Participants With Advanced Epithelial Ovarian Cancer
NCT03024437PHASE1/PHASE2TERMINATEDAtezolizumab in Combination With Entinostat and Bevacizumab in Patients With Advanced Renal Cell Carcinoma
NCT03211988PHASE2TERMINATEDEntinostat Neuroendocrine (NE) Tumor
NCT03250273PHASE2COMPLETEDA Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma
NCT03280563PHASE1/PHASE2COMPLETEDA Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer
NCT03291886PHASE2COMPLETEDPhase 2 Study of KHK2375 in Subjects With Advanced or Recurrent Breast Cancer
NCT03552380PHASE2TERMINATEDStudy of Entinostat With Nivolumab Plus Ipilimumab in Previously Treated Renal Cell Carcinoma

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

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.

46 molecules share ≥1 primary target. Top 46 by shared-target count:

MoleculeSourceStatusShared targets
BELINOSTATChEMBLPhase 4 (approved)HDAC1, HDAC2, HDAC3, HDAC9
CELECOXIBChEMBLPhase 4 (approved)HDAC1, HDAC2, HDAC3, HDAC9
GIVINOSTATChEMBLPhase 4 (approved)HDAC1, HDAC2, HDAC3, HDAC9
PANOBINOSTATChEMBLPhase 4 (approved)HDAC1, HDAC2, HDAC3, HDAC9
PHENYLBUTANOIC ACIDChEMBLPhase 4 (approved)HDAC1, HDAC2, HDAC3, HDAC9
ROMIDEPSINChEMBLPhase 4 (approved)HDAC1, HDAC2, HDAC3, HDAC9
SODIUM PHENYLBUTYRATEChEMBLPhase 4 (approved)HDAC1, HDAC2, HDAC3, HDAC9
VORINOSTATChEMBLPhase 4 (approved)HDAC1, HDAC2, HDAC3, HDAC9
ABEXINOSTATChEMBLPhase 3HDAC1, HDAC2, HDAC3, HDAC9
CAFFEIC ACIDChEMBLPhase 3HDAC1, HDAC2, HDAC3, HDAC9
CURCUMINChEMBLPhase 3HDAC1, HDAC2, HDAC3, HDAC9
PRACINOSTATChEMBLPhase 3HDAC1, HDAC2, HDAC3, HDAC9
TACEDINALINEChEMBLPhase 3HDAC1, HDAC2, HDAC3, HDAC9
TUCIDINOSTATChEMBLPhase 3HDAC1, HDAC2, HDAC3, HDAC9
AR-42ChEMBLPhase 2HDAC1, HDAC2, HDAC3, HDAC9
CHLOROGENIC ACIDChEMBLPhase 2HDAC1, HDAC2, HDAC3, HDAC9
DACINOSTATChEMBLPhase 2HDAC1, HDAC2, HDAC3, HDAC9
DOMATINOSTATChEMBLPhase 2HDAC1, HDAC2, HDAC3, HDAC9
FIMEPINOSTATChEMBLPhase 2HDAC1, HDAC2, HDAC3, HDAC9
NANATINOSTATChEMBLPhase 2HDAC1, HDAC2, HDAC3, HDAC9
QUISINOSTATChEMBLPhase 2HDAC1, HDAC2, HDAC3, HDAC9
PazopanibPubChemApprovedHDAC1, HDAC2, HDAC3, HDAC9
BENDAMUSTINEChEMBLPhase 4 (approved)HDAC1, HDAC2, HDAC3
BORTEZOMIBChEMBLPhase 4 (approved)HDAC1, HDAC2, HDAC3
BUTYRIC ACIDChEMBLPhase 2HDAC1, HDAC2, HDAC3
CITARINOSTATChEMBLPhase 2HDAC1, HDAC2, HDAC3
MOCETINOSTATChEMBLPhase 2HDAC1, HDAC2, HDAC3
RICOLINOSTATChEMBLPhase 2HDAC1, HDAC2, HDAC3
SODIUM BUTYRATEChEMBLPhase 2HDAC1, HDAC2, HDAC3
TINOSTAMUSTINEChEMBLPhase 2HDAC1, HDAC2, HDAC3
ATORVASTATINChEMBLPhase 4 (approved)HDAC1, HDAC2
LOVASTATINChEMBLPhase 4 (approved)HDAC1, HDAC2
VALPROIC ACIDChEMBLPhase 4 (approved)HDAC1, HDAC2
EBSELENChEMBLPhase 3HDAC2, HDAC9
MOLIBRESIBChEMBLPhase 2HDAC1, HDAC2
CrizotinibPubChemApprovedHDAC1, HDAC2
DAUNORUBICINChEMBLPhase 4 (approved)HDAC1
EXIFONEChEMBLPhase 4 (approved)HDAC1
MOMELOTINIBChEMBLPhase 4 (approved)HDAC1
BAICALEINChEMBLPhase 2HDAC1
NICOXAMATChEMBLPhase 2HDAC1
RESMINOSTATChEMBLPhase 2HDAC1
.gamma.-aminobutyric acidPubChemApprovedHDAC9
acetylcysteinePubChemApprovedHDAC9
GefitinibPubChemApprovedHDAC9
IdelalisibPubChemApprovedHDAC1

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