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Enzastaurin

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Also known as DB-102DB102EnzastaurinaEnzastaurineKinenzaLy-317615LY317615SID137275839SID170465609SID144206918ENZASTAURIN (LY317615)Enzastaurin hydrochlorideÊEnzastaurin hydrochlorideÂ

Summary

Enzastaurin (CHEMBL300138) is a phase-3 clinical-stage small molecule targeting PRKCA, PRKCB, and PRKCG; indicated across 29 conditions including glioblastoma and non-hodgkin lymphoma; with CIViC clinical evidence for 1 variant-indication association (e.g. JAK1 OVEREXPRESSION in lung non-small cell carcinoma).

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 4 (PRKCA, PRKCB, PRKCG…)
  • Indications: 29 conditions
  • Clinical trials: 39
  • Precision-oncology evidence (CIViC): 1 variant–indication association
  • Chemistry: 515.6 Da · C32H29N5O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL300138
NameEnzastaurin
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID176167
Molecular formulaC32H29N5O2
Molecular weight515.6
InChIKeyAXRCEOKUDYDWLF-UHFFFAOYSA-N

SMILES: CN1C=C(C2=CC=CC=C21)C3=C(C(=O)NC3=O)C4=CN(C5=CC=CC=C54)C6CCN(CC6)CC7=CC=CC=N7

IUPAC name: 3-(1-methylindol-3-yl)-4-[1-[1-(pyridin-2-ylmethyl)piperidin-4-yl]indol-3-yl]pyrrole-2,5-dione

Also known as: DB-102, DB102, Enzastaurin, Enzastaurina, Enzastaurine, Kinenza, Ly-317615, LY-317615, LY317615, SID137275839, enzastaurin, SID170465609

Parent form; salt/anhydrous children: CHEMBL2107337

Patent coverage: 1,331 distinct patent families (3,209 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 3,068 (96%) 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
PRKCAprotein kinase C alphaInhibition6.10.7%P17252
PRKCBprotein kinase C betaInhibition7.520.1%P05771
PRKCGprotein kinase C gammaInhibition5.70%P05129
PRKCDprotein kinase C deltaInhibition60.2%Q05655

Broader ChEMBL bioactivity targets: 80 (assay-derived). Sample: Rhodopsin kinase GRK7, Homeodomain-interacting protein kinase 4, Serine/threonine-protein kinase ICK, Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma, Platelet-derived growth factor receptor beta, Mast/stem cell growth factor receptor Kit, Vascular endothelial growth factor receptor 3, Receptor-type tyrosine-protein kinase FLT3, Protein kinase C (PKC), CaM kinase II.

Bioactivity

ChEMBL activities: 115 potent at pChembl ≥ 5 of 115 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PRKCB8.22IC506nMCHEMBL_ACT_18668770
PRKCB8.22IC506nMCHEMBL_ACT_24893149
PRKCB8.22IC506nMCHEMBL_ACT_24954177
GSK3B8.08Kd8.3nMCHEMBL_ACT_24958023
GSK3B8.08Kd8.3nMCHEMBL_ACT_7582358
PRKCE8.05Kd8.9nMCHEMBL_ACT_7584435
PRKCD7.6Kd25nMCHEMBL_ACT_24958025
RPS6KA67.6Kd25nMCHEMBL_ACT_24958029
PRKCD7.6Kd25nMCHEMBL_ACT_7584469
RPS6KA67.6Kd25nMCHEMBL_ACT_7584504
PRKCB7.52IC5030nMCHEMBL_ACT_256023
PRKCB7.52IC5030nMCHEMBL_ACT_256024
PRKCQ7.44Kd36nMCHEMBL_ACT_24958027
PRKCQ7.44Kd36nMCHEMBL_ACT_7584472
PRKCA7.41IC5039nMCHEMBL_ACT_18668771
PRKCA7.41IC5039nMCHEMBL_ACT_24954176
FLT37.4Kd40nMCHEMBL_ACT_24958021
FLT37.4Kd40nMCHEMBL_ACT_7582441
PRKCH7.34Kd46nMCHEMBL_ACT_24958026
PRKCH7.34Kd46nMCHEMBL_ACT_7584470
FLT37.31Kd49nMCHEMBL_ACT_24958020
FLT37.31Kd49nMCHEMBL_ACT_7582440
FLT37.14Kd72nMCHEMBL_ACT_24958022
FLT37.14Kd72nMCHEMBL_ACT_7582442
MAPK157.12Kd76nMCHEMBL_ACT_24958024
MAPK157.12Kd76nMCHEMBL_ACT_7584585
PRKCG7.08IC5083nMCHEMBL_ACT_18668772
PRKCG7.08IC5083nMCHEMBL_ACT_24954178
RPS6KA37.06Kd87nMCHEMBL_ACT_24958028
RPS6KA37.06Kd87nMCHEMBL_ACT_7584381

Target pathways

Aggregated over 4 target gene(s): PRKCA, PRKCB, PRKCG, PRKCD.

Top Reactome pathways

97 total, by targets touching each:

PathwayTargetsGenes
Hemostasis4PRKCA, PRKCB, PRKCD, PRKCG
Signal Transduction4PRKCA, PRKCB, PRKCD, PRKCG
Signaling by GPCR4PRKCA, PRKCB, PRKCD, PRKCG
GPCR downstream signalling4PRKCA, PRKCB, PRKCD, PRKCG
G alpha (z) signalling events4PRKCA, PRKCB, PRKCD, PRKCG
Platelet activation, signaling and aggregation4PRKCA, PRKCB, PRKCD, PRKCG
Opioid Signalling3PRKCA, PRKCD, PRKCG
Calmodulin induced events3PRKCA, PRKCD, PRKCG
Ca-dependent events3PRKCA, PRKCD, PRKCG
CaM pathway3PRKCA, PRKCD, PRKCG
G-protein mediated events3PRKCA, PRKCD, PRKCG
PLC beta mediated events3PRKCA, PRKCD, PRKCG
Neurotransmitter receptors and postsynaptic signal transmission3PRKCA, PRKCB, PRKCG
Transmission across Chemical Synapses3PRKCA, PRKCB, PRKCG
Neuronal System3PRKCA, PRKCB, PRKCG
Disinhibition of SNARE formation3PRKCA, PRKCB, PRKCG
DAG and IP3 signaling3PRKCA, PRKCD, PRKCG
Signaling by VEGF3PRKCA, PRKCB, PRKCD
Signaling by Rho GTPases3PRKCA, PRKCB, PRKCD
RHO GTPase Effectors3PRKCA, PRKCB, PRKCD
Signaling by WNT3PRKCA, PRKCB, PRKCG
Beta-catenin independent WNT signaling3PRKCA, PRKCB, PRKCG
Trafficking of AMPA receptors3PRKCA, PRKCB, PRKCG
Glutamate binding, activation of AMPA receptors and synaptic plasticity3PRKCA, PRKCB, PRKCG
PCP/CE pathway3PRKCA, PRKCB, PRKCG
Trafficking of GluR2-containing AMPA receptors3PRKCA, PRKCB, PRKCG
G alpha (i) signalling events3PRKCA, PRKCD, PRKCG
VEGFA-VEGFR2 Pathway3PRKCA, PRKCB, PRKCD
WNT5A-dependent internalization of FZD43PRKCA, PRKCB, PRKCG
VEGFR2 mediated cell proliferation3PRKCA, PRKCB, PRKCD

Dominant GO biological processes

GO termTargets
protein phosphorylation4
intracellular signal transduction4
protein kinase C signaling3
apoptotic process3
mitotic nuclear membrane disassembly2
learning or memory2
response to toxic substance2
positive regulation of insulin secretion2
negative regulation of glial cell apoptotic process2
regulation of mRNA stability2
positive regulation of angiogenesis2
chromatin remodeling2
regulation of transport2
signal transduction2
negative regulation of insulin receptor signaling pathway2

Indications & clinical

Indications

29 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
glioblastoma3MONDO:0018177EFO:0000519
non-Hodgkin lymphoma3MONDO:0018908EFO:0005952
Ehlers-Danlos syndrome3MONDO:0020066MONDO:0020066
mantle cell lymphoma2MONDO:0018876EFO:1001469
lymphoma2MONDO:0005062EFO:0000574
neoplasm of mature B-cells2MONDO:0004949EFO:0000096
primary cutaneous T-cell non-Hodgkin lymphoma2MONDO:0000607EFO:0002913
colorectal adenocarcinoma2MONDO:0005008EFO:0000365
diffuse large B-cell lymphoma2MONDO:0018905EFO:0000403
renal cell carcinoma2MONDO:0005086EFO:0000681
small cell lung carcinoma2MONDO:0008433EFO:0000702
plasma cell myeloma2MONDO:0009693EFO:0001378
non-small cell lung carcinoma2MONDO:0005233EFO:0003060
pancreatic neoplasm2MONDO:0021040EFO:0003860
Waldenstrom macroglobulinemia2MONDO:0100280EFO:0009441
fallopian tube carcinoma2MONDO:0006206EFO:1000251
peritoneal neoplasm2MONDO:0006901EFO:1001100
breast neoplasm2MONDO:0021100MONDO:0007254
ovarian cancer2MONDO:0008170MONDO:0008170
lung neoplasm2MONDO:0021117MONDO:0008903
follicular lymphoma2MONDO:0018906MONDO:0018906
glioma2MONDO:0021042MONDO:0100342
neoplasm2MONDO:0005070EFO:0000616
colorectal neoplasm2MONDO:0005335MONDO:0005575
lymphoid leukemia1MONDO:0005402EFO:0004289
gliosarcoma1MONDO:0016681EFO:1001465
paraganglioma1MONDO:0000448EFO:1000453

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

Clinical trials

Total trials: 39.

Phase distribution

PhaseTrials
PHASE229
PHASE15
PHASE33
PHASE1/PHASE22

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00295815PHASE3COMPLETEDEnzastaurin Versus Lomustine in Glioblastoma
NCT00332202PHASE3COMPLETEDPRELUDE:Study to Investigate the Prevention of Relapse in Lymphoma Using Daily Enzastaurin
NCT05463679PHASE3SUSPENDEDInvestigate Efficacy, Safety, and Pharmacokinetics of Enzastaurin for the Prevention of Arterial Events in Patients With Vascular Ehlers-Danlos Syndrome.
NCT00042666PHASE2COMPLETEDA Study of Oral LY317615 in Relapsed or Refractory Diffuse Large B-Cell Lymphomas.
NCT00088205PHASE2COMPLETEDOral Enzastaurin in Participants With Relapsed Mantle Cell Lymphoma
NCT00190723PHASE2COMPLETEDA Study of LY317615 in Patients With Brain Tumors
NCT00267020PHASE2COMPLETEDPhase 2 Study of Gemcitabine or Gemcitabine + Enzastaurin in Participants With Advanced or Metastatic Pancreatic Cancer
NCT00308750PHASE2COMPLETEDFirst Line Chemotherapy Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
NCT00309140PHASE2COMPLETEDAn Open Label Study of Oral Enzastaurin in Participants With Cancer
NCT00391118PHASE2COMPLETEDComparing Two Treatments for Ovarian Cancer: Standard Chemotherapy Plus Enzastaurin, or Placebo (Sugar Pill)
NCT00402116PHASE1/PHASE2COMPLETEDPhase 1/2 Study of Enzastaurin in Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma (GS) Patients
NCT00414960PHASE2COMPLETEDA Trial of Placebo Versus Enzastaurin for Lung Cancer Prevention in Former Smokers
NCT00415363PHASE2COMPLETEDStudy of Enzastaurin Versus Placebo in the Treatment of Patients With Brain Metastases of Lung Cancer, After Whole Brain Radiation Therapy
NCT00420381PHASE2COMPLETEDEvaluation of Enzastaurin in the Treatment of Persistent or Recurrent Ovarian or Primary Peritoneal Cancer
NCT00428714PHASE2COMPLETEDPhase 2 Trial of Enzastaurin in Prostate Cancer in Participants Who Have Had Hormonal and Chemotherapy
NCT00436280PHASE2COMPLETEDChemotherapy for Participants With Lymphoma
NCT00437268PHASE2COMPLETEDA Study of Irinotecan Plus Cetuximab With or Without Enzastaurin in Participants With Colorectal Cancer
NCT00437294PHASE2TERMINATEDEnzastaurin in Combination of Capecitabine to Treat Breast Cancer
NCT00451178PHASE2COMPLETEDA Study of Participants With Lymphoma Who Take R-CHOP and Enzastaurin Compared to Participants Who Take R-CHOP Only
NCT00451555PHASE2COMPLETEDEnzastaurin Plus Fulvestrant vs. Placebo Plus Fulvestrant in Breast Cancer
NCT00452413PHASE1/PHASE2COMPLETEDA Study of Enzastaurin and Erlotinib in Participants With Solid Tumors and Lung Cancer
NCT00466440PHASE2COMPLETEDA Phase 2 Study With Enzastaurin Plus Chemotherapy or Placebo Plus Chemotherapy for Prostate Cancer Patients
NCT00475644PHASE2COMPLETEDA Study of Enzastaurin in Participants With Follicular Lymphoma
NCT00509821PHASE2COMPLETEDEnzastaurin Before and Concomitant With Radiation, Followed by Enzastaurin in Participants With Newly Diagnosed Glioblastoma
NCT00530621PHASE2COMPLETEDStudy of Enzastaurin Versus Placebo With Pemetrexed for Participants With Advanced or Metastatic Lung Cancer
NCT00533429PHASE2COMPLETEDStudy of Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin Versus Pemetrexed + Carboplatin + Bevacizumab + Placebo in Participants With Non-Small Cell Lung Cancer Who Have Not Been Previously Treated With Chemotherapy
NCT00536939PHASE2TERMINATEDTrial of Paclitaxel, Bevacizumab, and Enzastaurin Versus Paclitaxel, Bevacizumab and Placebo for Breast Cancer
NCT00538681PHASE2TERMINATEDStudy for Participants With Advanced, Not Amenable to Surgery, or Metastatic Lung Cancer Comparing Treatment With Pemetrexed + Cisplatin + Enzastaurin Versus Pemetrexed + Cisplatin + Placebo
NCT00542919PHASE2COMPLETEDA Study for Patients With Non-Hodgkin’s Lymphomas
NCT00586508PHASE2COMPLETEDTrial of Enzastaurin and Bevacizumab in Participants With Recurrent Malignant Gliomas
NCT00612586PHASE2COMPLETEDStudy of Enzastaurin With 5-Fluorouracil/Leucovorin (5-FU/LV) Plus Bevacizumab as Maintenance Regimen Following First Line Therapy for Metastatic Colon Cancer
NCT00709995PHASE2COMPLETEDA Study for Participants With Metastatic Renal Cell Carcinoma
NCT00718419PHASE2COMPLETEDA Study for Patients That Have Been Previously Been Treated in Waldenstrom’s Macroglobulinemia or Multiple Myeloma
NCT00744991PHASE2COMPLETEDA Study for Participants With Relapsed Cutaneous T-Cell Lymphoma
NCT00108056PHASE1TERMINATEDEnzastaurin to Treat Recurrent Brain Tumor
NCT00452257PHASE1COMPLETEDA Study of Enzastaurin in Patients With Leukemia
NCT01388335PHASE1COMPLETEDA Drug Interaction Study to Assess the Effect of LY317615 on the Metabolic Pathway of Warfarin
NCT01432951PHASE1COMPLETEDA Study of Enzastaurin in Chinese Patients With Advanced and/or Metastatic Solid Tumors or Lymphoma
NCT01445119PHASE1COMPLETEDA Phase I Trial of Enzastaurin (LY317615) in Combination With Carboplatin in Adults With Recurrent Gliomas

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
JAK1 OVEREXPRESSIONLung Non-small Cell CarcinomaSensitivity/ResponseEnzastaurinCIViC DEID931

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.

61 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
CAPIVASERTIBChEMBL + PubChemPhase 4 (approved)PRKCA, PRKCB, PRKCD, PRKCG
TAMOXIFENChEMBL + PubChemPhase 4 (approved)PRKCA, PRKCB, PRKCD, PRKCG
INGENOL MEBUTATEChEMBLPhase 4 (approved)PRKCA, PRKCB, PRKCD, PRKCG
MIDOSTAURINChEMBLPhase 4 (approved)PRKCA, PRKCB, PRKCD, PRKCG
ALVOCIDIBChEMBLPhase 3PRKCA, PRKCB, PRKCD, PRKCG
FASUDILChEMBLPhase 3PRKCA, PRKCB, PRKCD, PRKCG
RUBOXISTAURINChEMBLPhase 3PRKCA, PRKCB, PRKCD, PRKCG
SURAMINChEMBLPhase 3PRKCA, PRKCB, PRKCD, PRKCG
DAROVASERTIBChEMBLPhase 2PRKCA, PRKCB, PRKCD, PRKCG
EDELFOSINEChEMBLPhase 2PRKCA, PRKCB, PRKCD, PRKCG
PHORBOL MYRISTATEChEMBLPhase 2PRKCA, PRKCB, PRKCD, PRKCG
SOTRASTAURINChEMBLPhase 2PRKCA, PRKCB, PRKCD, PRKCG
UCN-01ChEMBLPhase 2PRKCA, PRKCB, PRKCD, PRKCG
UPROSERTIBChEMBLPhase 2PRKCA, PRKCB, PRKCD, PRKCG
BelzutifanPubChemApprovedPRKCA, PRKCB, PRKCD, PRKCG
IdelalisibPubChemApprovedPRKCA, PRKCB, PRKCD, PRKCG
ABEMACICLIBChEMBLPhase 4 (approved)PRKCA, PRKCB, PRKCD
BARICITINIBChEMBLPhase 4 (approved)PRKCA, PRKCB, PRKCD
DECERNOTINIBChEMBLPhase 2PRKCA, PRKCB, PRKCD
LY-2090314ChEMBLPhase 2PRKCB, PRKCD, PRKCG
ZOTIRACICLIBChEMBLPhase 2PRKCA, PRKCB, PRKCD
AfatinibPubChemApprovedPRKCA, PRKCB, PRKCD
BinimetinibPubChemApprovedPRKCA, PRKCB, PRKCD
CrizotinibPubChemApprovedPRKCA, PRKCB, PRKCD
dacomitinibPubChemApprovedPRKCA, PRKCB, PRKCD
FostamatinibPubChemApprovedPRKCA, PRKCB, PRKCD
GanciclovirPubChemApprovedPRKCB, PRKCD, PRKCG
PazopanibPubChemApprovedPRKCA, PRKCB, PRKCD
regorafenibPubChemApprovedPRKCA, PRKCB, PRKCD
SelumetinibPubChemApprovedPRKCA, PRKCB, PRKCD
TrametinibPubChemApprovedPRKCA, PRKCB, PRKCD
PACRITINIBChEMBLPhase 4 (approved)PRKCA, PRKCB
TOFACITINIBChEMBLPhase 4 (approved)PRKCA, PRKCD
AFURESERTIBChEMBLPhase 3PRKCA, PRKCB
LESTAURTINIBChEMBLPhase 3PRKCA, PRKCD
AT-9283ChEMBLPhase 2PRKCA, PRKCB
BMS-690514ChEMBLPhase 2PRKCA, PRKCD
BMS-754807ChEMBLPhase 2PRKCA, PRKCD
BRYOSTATIN 1ChEMBLPhase 2PRKCA, PRKCD
CENISERTIBChEMBLPhase 2PRKCD, PRKCG
DORAMAPIMODChEMBLPhase 2PRKCB, PRKCD
LAUROGUADINEChEMBLPhase 2PRKCD, PRKCG
R-406ChEMBLPhase 2PRKCD, PRKCG
GefitinibPubChemApprovedPRKCB, PRKCD
BOSUTINIBChEMBLPhase 4 (approved)PRKCD
ENTRECTINIBChEMBLPhase 4 (approved)PRKCG
GILTERITINIBChEMBLPhase 4 (approved)PRKCA
RUXOLITINIBChEMBLPhase 4 (approved)PRKCA
SUNITINIBChEMBLPhase 4 (approved)PRKCA
CRENOLANIBChEMBLPhase 3PRKCD
CURCUMINChEMBLPhase 3PRKCD
DOVITINIBChEMBLPhase 3PRKCD
RIPASUDILChEMBLPhase 3PRKCD
ACETOSIDEChEMBLPhase 2PRKCA
APITOLISIBChEMBLPhase 2PRKCA
ILORASERTIBChEMBLPhase 2PRKCD
PELITINIBChEMBLPhase 2PRKCD
SAR-407899 FREE BASEChEMBLPhase 2PRKCD
SCH-900776ChEMBLPhase 2PRKCD
CobimetinibPubChemApprovedPRKCG

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