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Entospletinib

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Also known as GS-9973SYK INHIBITOR GS-9973GS9973CPD 68CG9ENTOSPLETINIB DIMESYLATEENTOSPLETINIB (GS-9973)

Summary

Entospletinib (CHEMBL3265032) is a phase-3 clinical-stage small molecule targeting SYK; indicated across 9 conditions including acute myeloid leukemia and b-cell chronic lymphocytic leukemia.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 1 (SYK)
  • Indications: 9 conditions
  • Clinical trials: 12
  • Chemistry: 411.5 Da · C23H21N7O

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL3265032
NameEntospletinib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID59473233
Molecular formulaC23H21N7O
Molecular weight411.5
InChIKeyXSMSNFMDVXXHGJ-UHFFFAOYSA-N

SMILES: C1COCCN1C2=CC=C(C=C2)NC3=NC(=CN4C3=NC=C4)C5=CC6=C(C=C5)C=NN6

IUPAC name: 6-(1H-indazol-6-yl)-N-(4-morpholin-4-ylphenyl)imidazo[1,2-a]pyrazin-8-amine

Also known as: Entospletinib, GS-9973, SYK INHIBITOR GS-9973, ENTOSPLETINIB, GS9973, CPD 68, CG9, ENTOSPLETINIB DIMESYLATE, ENTOSPLETINIB (GS-9973), Entospletinib (GS-9973)

Patent coverage: 497 distinct patent families (1,628 SureChEMBL compound mentions), from 2 matched compound structure(s). 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
SYKspleen associated tyrosine kinaseInhibition8.112%P43405

Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: Receptor-type tyrosine-protein kinase FLT3, Mast/stem cell growth factor receptor Kit, Tyrosine-protein kinase SYK, High affinity nerve growth factor receptor, Tyrosine-protein kinase JAK2, Casein kinase 2, Tyrosine-protein kinase SYK, Protein-tyrosine kinase 6, Tyrosine-protein kinase BTK, Proto-oncogene tyrosine-protein kinase ROS.

Bioactivity

ChEMBL activities: 29 potent at pChembl ≥ 5 of 30 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
SYK8.7EC502nMCHEMBL_ACT_20609093
SYK8.11IC507.7nMCHEMBL_ACT_14671986
SYK8.11IC507.7nMCHEMBL_ACT_25497181
SYK7.99IC5010.3nMCHEMBL_ACT_26145239
SYK7.96IC5011nMCHEMBL_ACT_24752228
SYK7.96IC5011nMCHEMBL_ACT_26148016
SYK7.78IC5016.5nMCHEMBL_ACT_20609057
SYK7.78IC5016.5nMCHEMBL_ACT_25638895
SYK7.58EC5026nMCHEMBL_ACT_14672029
SYK7.46IC5035nMCHEMBL_ACT_25879192
SYK7.39EC5041nMCHEMBL_ACT_14672078
SYK7.09IC5082nMCHEMBL_ACT_22982176
SYK6.9EC50125nMCHEMBL_ACT_14672076
JAK26.84IC50143nMCHEMBL_ACT_25879210
SYK6.83IC50147nMCHEMBL_ACT_14672080
SYK6.75EC50178nMCHEMBL_ACT_20609129
FLT36.52IC50303nMCHEMBL_ACT_25879197
FLT36.49EC50327nMCHEMBL_ACT_14672070
SYK6.43EC50367nMCHEMBL_ACT_14672046
SYK6.42IC50377nMCHEMBL_ACT_15225264
P055326.35EC50445nMCHEMBL_ACT_14672068
JAK26.34EC50453nMCHEMBL_ACT_14672066
NTRK16.25IC50569nMCHEMBL_ACT_25879205
CSNK2A26.22IC50604nMCHEMBL_ACT_25879211
BTK6.1IC50801nMCHEMBL_ACT_22982182
PTK66.08IC50842nMCHEMBL_ACT_25879212
ROS16.07IC50857nMCHEMBL_ACT_25879195
SYK6.06IC50878nMCHEMBL_ACT_15224040
Q647255.72EC501900nMCHEMBL_ACT_14672714

Target pathways

Aggregated over 1 target gene(s): SYK.

Top Reactome pathways

47 total, by targets touching each:

PathwayTargetsGenes
Hemostasis1SYK
GPVI-mediated activation cascade1SYK
Cytokine Signaling in Immune system1SYK
Adaptive Immune System1SYK
Signal Transduction1SYK
Disease1SYK
Innate Immune System1SYK
Immune System1SYK
Fcgamma receptor (FCGR) dependent phagocytosis1SYK
FCGR activation1SYK
Regulation of actin dynamics for phagocytic cup formation1SYK
Role of phospholipids in phagocytosis1SYK
DAP12 interactions1SYK
DAP12 signaling1SYK
Fc epsilon receptor (FCERI) signaling1SYK
Role of LAT2/NTAL/LAB on calcium mobilization1SYK
FCERI mediated MAPK activation1SYK
FCERI mediated Ca+2 mobilization1SYK
Integrin signaling1SYK
Signaling by Interleukins1SYK
Interleukin-2 family signaling1SYK
Interleukin-3, Interleukin-5 and GM-CSF signaling1SYK
CLEC7A (Dectin-1) signaling1SYK
Dectin-2 family1SYK
C-type lectin receptors (CLRs)1SYK
Infectious disease1SYK
Platelet activation, signaling and aggregation1SYK
Platelet Aggregation (Plug Formation)1SYK
Interleukin-2 signaling1SYK
Regulation of signaling by CBL1SYK
FLT3 Signaling1SYK
Leishmania infection1SYK
Anti-inflammatory response favouring Leishmania parasite infection1SYK
FCGR3A-mediated IL10 synthesis1SYK
Parasite infection1SYK
Leishmania phagocytosis1SYK
FCGR3A-mediated phagocytosis1SYK
Leishmania parasite growth and survival1SYK
Signaling by CSF3 (G-CSF)1SYK
Potential therapeutics for SARS1SYK
SARS-CoV Infections1SYK
Inactivation of CSF3 (G-CSF) signaling1SYK
FLT3 signaling through SRC family kinases1SYK
Parasitic Infection Pathways1SYK
Viral Infection Pathways1SYK
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers1SYK
Signaling by the B Cell Receptor (BCR)1SYK

Dominant GO biological processes

GO termTargets
angiogenesis1
cell activation1
lymph vessel development1
positive regulation of receptor internalization1
stimulatory C-type lectin receptor signaling pathway1
adaptive immune response1
macrophage activation involved in immune response1
neutrophil activation involved in immune response1
leukocyte activation involved in immune response1
serotonin secretion by platelet1
cell surface pattern recognition receptor signaling pathway1
negative regulation of inflammatory response to antigenic stimulus1
protein phosphorylation1
protein import into nucleus1
leukocyte cell-cell adhesion1

Indications & clinical

Indications

9 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)PhaseMONDOEFO
acute myeloid leukemia3MONDO:0018874EFO:0000222
B-cell chronic lymphocytic leukemia2MONDO:0004948EFO:0000095
diffuse large B-cell lymphoma2MONDO:0018905EFO:0000403
mantle cell lymphoma2MONDO:0018876EFO:1001469
non-Hodgkin lymphoma2MONDO:0018908EFO:0005952
follicular lymphoma2MONDO:0018906MONDO:0018906
lymphoma2MONDO:0005062EFO:0000574
acute lymphoblastic leukemia1MONDO:0004967EFO:0000220
neoplasm1MONDO:0005070MONDO:0004992

Clinical trials

Total trials: 12.

Phase distribution

PhaseTrials
PHASE1/PHASE26
PHASE13
PHASE22
PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05020665PHASE3TERMINATEDEntospletinib Plus Intensive Induction/Consolidation Chemotherapy in Newly Diagnosed NPM1-mutated AML
NCT03013998PHASE1/PHASE2RECRUITINGStudy of Biomarker-Based Treatment of Acute Myeloid Leukemia
NCT01796470PHASE2TERMINATEDEntospletinib in Combination With Idelalisib in Adults With Relapsed or Refractory Hematologic Malignancies
NCT02343939PHASE1/PHASE2TERMINATEDEntospletinib Monotherapy and in Combination With Chemotherapy in Adults With Acute Myeloid Leukemia (AML)
NCT02404220PHASE1/PHASE2TERMINATEDSafety and Efficacy of Entospletinib With Vincristine and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
NCT02568683PHASE1/PHASE2TERMINATEDSafety and Efficacy of Entospletinib (ENTO [GS-9973]) Combined With Vincristine (VCR) in Adult Participants With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (NHL)
NCT02983617PHASE2COMPLETEDSafety and Efficacy of the Combination of Tirabrutinib and Entospletinib With and Without Obinutuzumab in Adults With Chronic Lymphocytic Leukemia (CLL)
NCT03010358PHASE1/PHASE2COMPLETEDEntospletinib and Obinutuzumab in Treating Patients With Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma
NCT03225924PHASE1/PHASE2TERMINATEDStudy of Entospletinib (ENTO) in Newly Diagnosed DLBCL Patients With aaIPI>=1 Treated by Chemiotherapy
NCT02457598PHASE1TERMINATEDDose Escalation and Dose Expansion Study of Tirabrutinib in Combination With Other Targeted Anti-cancer Therapies in Adults With B-cell Malignancies
NCT02521376PHASE1COMPLETEDPharmacokinetics of Entospletinib in Adults With Normal and Impaired Liver Function
NCT03135028PHASE1TERMINATEDEntospletinib (ENTO) as Monotherapy and in Combination With Chemotherapy in Japanese Adults

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.

53 molecules share ≥1 primary target. Top 53 by shared-target count:

MoleculeSourceStatusShared targets
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)SYK
FOSTAMATINIBChEMBL + PubChemPhase 4 (approved)SYK
PAZOPANIBChEMBL + PubChemPhase 4 (approved)SYK
BOSUTINIBChEMBLPhase 4 (approved)SYK
CERITINIBChEMBLPhase 4 (approved)SYK
DASATINIBChEMBLPhase 4 (approved)SYK
ENTRECTINIBChEMBLPhase 4 (approved)SYK
ERLOTINIBChEMBLPhase 4 (approved)SYK
FEDRATINIBChEMBLPhase 4 (approved)SYK
FOSTAMATINIB DISODIUMChEMBLPhase 4 (approved)SYK
GILTERITINIBChEMBLPhase 4 (approved)SYK
IMATINIBChEMBLPhase 4 (approved)SYK
INFIGRATINIBChEMBLPhase 4 (approved)SYK
MIDOSTAURINChEMBLPhase 4 (approved)SYK
NERATINIBChEMBLPhase 4 (approved)SYK
CEDIRANIBChEMBLPhase 3SYK
LESTAURTINIBChEMBLPhase 3SYK
QUERCETINChEMBLPhase 3SYK
ADAVOSERTIBChEMBLPhase 2SYK
APITOLISIBChEMBLPhase 2SYK
AT-9283ChEMBLPhase 2SYK
BERZOSERTIBChEMBLPhase 2SYK
BI-2536ChEMBLPhase 2SYK
CENISERTIBChEMBLPhase 2SYK
CERDULATINIBChEMBLPhase 2SYK
DANUSERTIBChEMBLPhase 2SYK
FISETINChEMBLPhase 2SYK
FORETINIBChEMBLPhase 2SYK
GENISTEINChEMBLPhase 2SYK
GLESATINIBChEMBLPhase 2SYK
GUSACITINIBChEMBLPhase 2SYK
ILORASERTIBChEMBLPhase 2SYK
LANRAPLENIBChEMBLPhase 2SYK
LUTEOLINChEMBLPhase 2SYK
MIVAVOTINIBChEMBLPhase 2SYK
PELITINIBChEMBLPhase 2SYK
R-112ChEMBLPhase 2SYK
R-343ChEMBLPhase 2SYK
R-406ChEMBLPhase 2SYK
RAF-265ChEMBLPhase 2SYK
REBASTINIBChEMBLPhase 2SYK
TOP-1288ChEMBLPhase 2SYK
TOZASERTIBChEMBLPhase 2SYK
UCN-01ChEMBLPhase 2SYK
AfatinibPubChemApprovedSYK
belumosudilPubChemApprovedSYK
BinimetinibPubChemApprovedSYK
dacomitinibPubChemApprovedSYK
GefitinibPubChemApprovedSYK
IdelalisibPubChemApprovedSYK
regorafenibPubChemApprovedSYK
SelumetinibPubChemApprovedSYK
TrametinibPubChemApprovedSYK

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
v1.1.4
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