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Ruboxistaurin

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Also known as ArxxantLy-333531RuboxistaurinaRuboxistaurineK00587aNARUBOXISTAURIN HYDROCHLORIDE

Summary

Ruboxistaurin (CHEMBL91829) is a phase-3 clinical-stage small molecule targeting PRKCA, PRKCB, and PRKCG; indicated across 6 conditions including diabetic retinopathy and diabetic neuropathy.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 6 (PRKCA, PRKCB, PRKCG…)
  • Indications: 6 conditions
  • Clinical trials: 13
  • Chemistry: 468.5 Da · C28H28N4O3

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL91829
NameRuboxistaurin
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID153999
Molecular formulaC28H28N4O3
Molecular weight468.5
InChIKeyZCBUQCWBWNUWSU-SFHVURJKSA-N

SMILES: CN(C)C[C@@H]1CCN2C=C(C3=CC=CC=C32)C4=C(C5=CN(CCO1)C6=CC=CC=C65)C(=O)NC4=O

IUPAC name: (18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione

Also known as: Arxxant, Ly-333531, Ruboxistaurin, Ruboxistaurina, Ruboxistaurine, ruboxistaurin, LY-333531, K00587a, RUBOXISTAURIN, NA, RUBOXISTAURIN HYDROCHLORIDE

Parent form; salt/anhydrous children: CHEMBL432130, CHEMBL5307356

Patent coverage: 44 distinct patent families (77 SureChEMBL compound mentions), from 1 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
PRKCAprotein kinase C alphaInhibition6.440.7%P17252
PRKCBprotein kinase C betaInhibition8.230.1%P05771
PRKCGprotein kinase C gammaInhibition6.520%P05129
PRKCDprotein kinase C deltaInhibition6.60.2%Q05655
PIM1Pim-1 proto-oncogene, serine/threonine kinaseInhibition6.7P11309
PIM2Pim-2 proto-oncogene, serine/threonine kinaseInhibition4.73.8%Q9P1W9

Broader ChEMBL bioactivity targets: 122 (assay-derived). Sample: Leucine-rich repeat serine/threonine-protein kinase 2, Rhodopsin kinase GRK7, Homeodomain-interacting protein kinase 4, Serine/threonine-protein kinase TAO2, Cyclin-dependent kinase-like 5, Serine/threonine-protein kinase ICK, Serine/threonine-protein kinase PRP4 homolog, Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma, Platelet-derived growth factor receptor beta, Mast/stem cell growth factor receptor Kit.

Bioactivity

ChEMBL activities: 266 potent at pChembl ≥ 5 of 268 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PRKCQ8.6Kd2.5nMCHEMBL_ACT_2905475
PRKCQ8.6Kd2.5nMCHEMBL_ACT_7586814
PRKCD8.44Kd3.6nMCHEMBL_ACT_2905361
PRKCD8.44Kd3.6nMCHEMBL_ACT_7586811
PRKCB8.33IC504.7nMCHEMBL_ACT_1153805
PRKCB8.33IC504.7nMCHEMBL_ACT_1451452
PRKCB8.33IC504.7nMCHEMBL_ACT_18668763
PRKCB8.33IC504.7nMCHEMBL_ACT_24893141
PRKCB8.23IC505.9nMCHEMBL_ACT_1153806
PRKCB8.23IC505.9nMCHEMBL_ACT_1451453
PRKCB8.23IC505.9nMCHEMBL_ACT_18668764
PRKCB8.23IC505.9nMCHEMBL_ACT_24893142
PRKCB8.22IC506nMCHEMBL_ACT_939607
PRKCE7.96Kd11nMCHEMBL_ACT_2905399
PRKCE7.96Kd11nMCHEMBL_ACT_7586777
PIM37.92Kd12nMCHEMBL_ACT_2899312
PIM37.92Kd12nMCHEMBL_ACT_7584661
PRKCA7.64Kd23nMCHEMBL_ACT_17929743
MAP3K197.32Kd48nMCHEMBL_ACT_7586903
PIM17.3Kd50nMCHEMBL_ACT_12139747
PRKCH7.28IC5052nMCHEMBL_ACT_1153811
PIM17.26Kd55nMCHEMBL_ACT_1650050
PRKCD7.17Kd67nMCHEMBL_ACT_17930263
HIPK37.11Kd77nMCHEMBL_ACT_7586786
MAPK157.06Kd88nMCHEMBL_ACT_2906239
MAPK157.06Kd88nMCHEMBL_ACT_7586927
Q9JI107.05Kd90nMCHEMBL_ACT_1650572
TAOK37.01Kd97nMCHEMBL_ACT_7586866
HIPK17IC50100nMCHEMBL_ACT_22933211
HIPK27IC50100nMCHEMBL_ACT_22933215

Target pathways

Aggregated over 6 target gene(s): PRKCA, PRKCB, PRKCG, PRKCD, PIM1, PIM2.

Top Reactome pathways

101 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 phosphorylation6
apoptotic process5
intracellular signal transduction4
protein kinase C signaling3
positive regulation of DNA-templated transcription3
protein stabilization3
negative regulation of 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

Indications & clinical

Indications

6 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
diabetic retinopathy3MONDO:0005266EFO:0003770
diabetic neuropathy3MONDO:0006626EFO:1000783
type 1 diabetes mellitus3MONDO:0005147MONDO:0005147
diabetes mellitus2MONDO:0005015EFO:0000400
type 2 diabetes mellitus2MONDO:0005148MONDO:0005148
heart failure1MONDO:0005252EFO:0003144

Clinical trials

Total trials: 13.

Phase distribution

PhaseTrials
PHASE38
PHASE22
PHASE2/PHASE31
PHASE1/PHASE21
PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00044395PHASE3COMPLETEDTreatment for Symptomatic Peripheral Neuropathy in Patients With Diabetes
NCT00044408PHASE3COMPLETEDTreatment for Symptomatic Peripheral Neuropathy in Patients With Diabetes
NCT00044421PHASE3COMPLETEDTreatment of Peripheral Neuropathy in Patients With Diabetes
NCT00090519PHASE3COMPLETEDReduction in the Occurrence of Center-Involved Diabetic Macular Edema
NCT00133952PHASE3COMPLETEDEffect of Ruboxistaurin on Clinically Significant Macular Edema
NCT00266695PHASE3COMPLETEDTreatment for Completers of the Study B7A-MC-MBCM
NCT00297401PHASE3COMPLETEDRenal and Peripheral Hemodynamic Function in Patients With Type 1 Diabetes Mellitus
NCT00604383PHASE3COMPLETEDProtein Kinase C (PKC) Inhibitor-Diabetic Retinopathy Phase 3 Study
NCT00761852PHASE2/PHASE3COMPLETEDSignaling Mechanisms and Vascular Function in Diabetes Mellitus
NCT00190970PHASE2COMPLETEDThe Effect of Ruboxistaurin on Small Fiber Function
NCT00482976PHASE2COMPLETEDEffect of LY333531 on Vascular and Neural Functions
NCT02769611PHASE1/PHASE2WITHDRAWNRuboxistaurin in New York Heart Failure Classification III-IV Patients
NCT00552227PHASE1COMPLETEDIsoprostane/FMD Study The Effect of Protein Kinase C (PKC) β Specific Inhibitor LY333531 on Oxidant Stress in Patients With Type 2 Diabetes Mellitus

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.

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

MoleculeSourceStatusShared targets
MIDOSTAURINChEMBLPhase 4 (approved)PIM1, PIM2, PRKCA, PRKCB, PRKCD, PRKCG
ALVOCIDIBChEMBLPhase 3PIM1, PIM2, PRKCA, PRKCB, PRKCD, PRKCG
ENZASTAURINChEMBLPhase 3PIM1, PIM2, PRKCA, PRKCB, PRKCD, PRKCG
SOTRASTAURINChEMBLPhase 2PIM1, PIM2, PRKCA, PRKCB, PRKCD, PRKCG
IdelalisibPubChemApprovedPIM1, PIM2, PRKCA, PRKCB, PRKCD, PRKCG
ABEMACICLIBChEMBLPhase 4 (approved)PIM1, PIM2, PRKCA, PRKCB, PRKCD
AfatinibPubChemApprovedPIM1, PIM2, PRKCA, PRKCB, PRKCD
BinimetinibPubChemApprovedPIM1, PIM2, PRKCA, PRKCB, PRKCD
CrizotinibPubChemApprovedPIM1, PIM2, PRKCA, PRKCB, PRKCD
dacomitinibPubChemApprovedPIM1, PIM2, PRKCA, PRKCB, PRKCD
PazopanibPubChemApprovedPIM1, PIM2, PRKCA, PRKCB, PRKCD
regorafenibPubChemApprovedPIM1, PIM2, PRKCA, PRKCB, PRKCD
SelumetinibPubChemApprovedPIM1, PIM2, PRKCA, PRKCB, PRKCD
TrametinibPubChemApprovedPIM1, PIM2, PRKCA, PRKCB, PRKCD
CAPIVASERTIBChEMBL + PubChemPhase 4 (approved)PRKCA, PRKCB, PRKCD, PRKCG
GefitinibChEMBL + PubChemPhase 4 (approved)PIM1, PIM2, PRKCB, PRKCD
TAMOXIFENChEMBL + PubChemPhase 4 (approved)PRKCA, PRKCB, PRKCD, PRKCG
INGENOL MEBUTATEChEMBLPhase 4 (approved)PRKCA, PRKCB, PRKCD, PRKCG
FASUDILChEMBLPhase 3PRKCA, PRKCB, PRKCD, PRKCG
LESTAURTINIBChEMBLPhase 3PIM1, PIM2, PRKCA, PRKCD
SURAMINChEMBLPhase 3PRKCA, PRKCB, PRKCD, PRKCG
DAROVASERTIBChEMBLPhase 2PRKCA, PRKCB, PRKCD, PRKCG
EDELFOSINEChEMBLPhase 2PRKCA, PRKCB, PRKCD, PRKCG
LY-2090314ChEMBLPhase 2PIM1, PRKCB, PRKCD, PRKCG
PHORBOL MYRISTATEChEMBLPhase 2PRKCA, PRKCB, PRKCD, PRKCG
UCN-01ChEMBLPhase 2PRKCA, PRKCB, PRKCD, PRKCG
UPROSERTIBChEMBLPhase 2PRKCA, PRKCB, PRKCD, PRKCG
BelzutifanPubChemApprovedPRKCA, PRKCB, PRKCD, PRKCG
FostamatinibPubChemApprovedPIM1, PRKCA, PRKCB, PRKCD
BARICITINIBChEMBLPhase 4 (approved)PRKCA, PRKCB, PRKCD
DECERNOTINIBChEMBLPhase 2PRKCA, PRKCB, PRKCD
LAUROGUADINEChEMBLPhase 2PIM1, PRKCD, PRKCG
ZOTIRACICLIBChEMBLPhase 2PRKCA, PRKCB, PRKCD
GanciclovirPubChemApprovedPRKCB, PRKCD, PRKCG
PACRITINIBChEMBLPhase 4 (approved)PRKCA, PRKCB
SUNITINIBChEMBLPhase 4 (approved)PIM2, PRKCA
TOFACITINIBChEMBLPhase 4 (approved)PRKCA, PRKCD
AFURESERTIBChEMBLPhase 3PRKCA, PRKCB
DOVITINIBChEMBLPhase 3PIM2, PRKCD
AT-9283ChEMBLPhase 2PRKCA, PRKCB
BMS-690514ChEMBLPhase 2PRKCA, PRKCD
BMS-754807ChEMBLPhase 2PRKCA, PRKCD
BRYOSTATIN 1ChEMBLPhase 2PRKCA, PRKCD
CENISERTIBChEMBLPhase 2PRKCD, PRKCG
DAPOLSERTIBChEMBLPhase 2PIM1, PIM2
DORAMAPIMODChEMBLPhase 2PRKCB, PRKCD
NUVISERTIBChEMBLPhase 2PIM1, PIM2
R-406ChEMBLPhase 2PRKCD, PRKCG
SCH-900776ChEMBLPhase 2PIM1, PRKCD
SILMITASERTIBChEMBLPhase 2PIM1, PIM2
belumosudilPubChemApprovedPIM1, PIM2
ImatinibPubChemApprovedPIM1, PIM2
BOSUTINIBChEMBLPhase 4 (approved)PRKCD
COLCHICINEChEMBLPhase 4 (approved)PIM1
ENTRECTINIBChEMBLPhase 4 (approved)PRKCG
GILTERITINIBChEMBLPhase 4 (approved)PRKCA
LEFLUNOMIDEChEMBLPhase 4 (approved)PIM1
MITOXANTRONEChEMBLPhase 4 (approved)PIM1
RUCAPARIBChEMBLPhase 4 (approved)PIM1
RUXOLITINIBChEMBLPhase 4 (approved)PRKCA

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