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Lestaurtinib

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Also known as A-154475A-154475.0CEP-701KT-555KT-5555KT5555SP-924SP924SPM-924SID50113274SID144206186CEP701

Summary

Lestaurtinib (CHEMBL603469) is a phase-3 clinical-stage small molecule targeting LATS1, LATS2, and FLT3; indicated across 10 conditions including acute lymphoblastic leukemia and acute myeloid leukemia.

At a glance

  • Status: Max clinical phase 3 (not approved)
  • Modality: Small molecule
  • Targets: 3 (LATS1, LATS2, FLT3)
  • Indications: 10 conditions
  • Clinical trials: 11
  • Chemistry: 439.5 Da · C26H21N3O4

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL603469
NameLestaurtinib
TypeSmall molecule
Max phase3
FDA approvedno
PubChem CID126565
Molecular formulaC26H21N3O4
Molecular weight439.5
InChIKeyUIARLYUEJFELEN-LROUJFHJSA-N

SMILES: C[C@@]12[C@](C[C@@H](O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)(CO)O

IUPAC name: (15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one

Also known as: A-154475, A-154475.0, CEP-701, KT-555, KT-5555, KT5555, Lestaurtinib, SP-924, SP924, SPM-924, SID50113274, LESTAURTINIB

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
LATS1large tumor suppressor kinase 1Inhibition7.520.1%O95835
LATS2large tumor suppressor kinase 2Inhibition90.6%Q9NRM7
FLT3fms related receptor tyrosine kinase 3Inhibition8.070.9%P36888

Broader ChEMBL bioactivity targets: 358 (assay-derived). Sample: Leucine-rich repeat serine/threonine-protein kinase 2, Rhodopsin kinase GRK7, Serine/threonine-protein kinase 38, Homeodomain-interacting protein kinase 4, Serine/threonine-protein kinase TAO2, Serine/threonine-protein kinase/endoribonuclease IRE1, Serine/threonine-protein kinase OSR1, Serine/threonine-protein kinase MAK, STE20/SPS1-related proline-alanine-rich protein kinase, Cyclin-dependent kinase-like 5.

Bioactivity

ChEMBL activities: 866 potent at pChembl ≥ 5 of 869 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
PHKG19.41Kd0.39nMCHEMBL_ACT_3445241
PHKG19.41Kd0.39nMCHEMBL_ACT_7589823
MAP3K199.28Kd0.52nMCHEMBL_ACT_3448831
MAP3K199.28Kd0.52nMCHEMBL_ACT_7589928
FLT39.24Kd0.57nMCHEMBL_ACT_3445125
FLT39.24Kd0.57nMCHEMBL_ACT_7589724
FLT39.18Kd0.66nMCHEMBL_ACT_3445124
FLT39.18Kd0.66nMCHEMBL_ACT_7589723
JAK29.05IC500.9nMCHEMBL_ACT_24788508
JAK29.05IC500.9nMCHEMBL_ACT_25555231
JAK29IC501nMCHEMBL_ACT_24975315
JAK29IC501nMCHEMBL_ACT_26309192
LATS29Kd1nMCHEMBL_ACT_3445168
NUAK29Kd1nMCHEMBL_ACT_3448785
LATS29Kd1nMCHEMBL_ACT_7589873
NUAK29Kd1nMCHEMBL_ACT_7589931
JAK38.96Kd1.1nMCHEMBL_ACT_25839827
FLT38.85Kd1.4nMCHEMBL_ACT_3445128
MKNK28.85Kd1.4nMCHEMBL_ACT_3445205
FLT38.85Kd1.4nMCHEMBL_ACT_7589727
MKNK28.85Kd1.4nMCHEMBL_ACT_7589898
Q003428.82IC501.5nMCHEMBL_ACT_14545494
FLT38.82IC501.5nMCHEMBL_ACT_3444909
PLK48.82Kd1.5nMCHEMBL_ACT_3445263
FLT38.82Kd1.5nMCHEMBL_ACT_7589725
PLK48.82Kd1.5nMCHEMBL_ACT_7589866
PHKG28.77Kd1.7nMCHEMBL_ACT_3445242
PHKG28.77Kd1.7nMCHEMBL_ACT_7588053
IRAK48.77Kd1.7nMCHEMBL_ACT_7589888
PKN28.74Kd1.8nMCHEMBL_ACT_3445259

Target pathways

Aggregated over 3 target gene(s): LATS1, LATS2, FLT3.

Top Reactome pathways

29 total, by targets touching each:

PathwayTargetsGenes
Signal Transduction2LATS1, LATS2
Signaling by Hippo2LATS1, LATS2
PI3K Cascade1FLT3
PIP3 activates AKT signaling1FLT3
Constitutive Signaling by Aberrant PI3K in Cancer1FLT3
RAF/MAP kinase cascade1FLT3
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling1FLT3
FLT3 Signaling1FLT3
STAT5 Activation1FLT3
FLT3 mutants bind TKIs1FLT3
STAT5 activation downstream of FLT3 ITD mutants1FLT3
KW2449-resistant FLT3 mutants1FLT3
semaxanib-resistant FLT3 mutants1FLT3
crenolanib-resistant FLT3 mutants1FLT3
gilteritinib-resistant FLT3 mutants1FLT3
lestaurtinib-resistant FLT3 mutants1FLT3
midostaurin-resistant FLT3 mutants1FLT3
pexidartinib-resistant FLT3 mutants1FLT3
ponatinib-resistant FLT3 mutants1FLT3
quizartinib-resistant FLT3 mutants1FLT3
sorafenib-resistant FLT3 mutants1FLT3
sunitinib-resistant FLT3 mutants1FLT3
tandutinib-resistant FLT3 mutants1FLT3
linifanib-resistant FLT3 mutants1FLT3
tamatinib-resistant FLT3 mutants1FLT3
Signaling by FLT3 ITD and TKD mutants1FLT3
Negative regulation of FLT31FLT3
FLT3 signaling through SRC family kinases1FLT3
FLT3 signaling by CBL mutants1FLT3

Dominant GO biological processes

GO termTargets
protein phosphorylation3
G1/S transition of mitotic cell cycle2
inner cell mass cell fate commitment2
inner cell mass cellular morphogenesis2
intracellular protein localization2
hormone-mediated signaling pathway2
regulation of transforming growth factor beta receptor signaling pathway2
keratinocyte differentiation2
hippo signaling2
positive regulation of apoptotic process2
negative regulation of cyclin-dependent protein serine/threonine kinase activity2
regulation of organ growth2
cell division2
negative regulation of canonical Wnt signaling pathway2
negative regulation of protein localization to nucleus2

Indications & clinical

Indications

10 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
acute lymphoblastic leukemia3MONDO:0004967EFO:0000220
acute myeloid leukemia2MONDO:0018874EFO:0000222
leukemia2MONDO:0005059EFO:0000565
psoriasis2MONDO:0005083EFO:0000676
essential thrombocythemia2MONDO:0005029EFO:0000479
plasma cell myeloma2MONDO:0009693EFO:0001378
acquired polycythemia vera2MONDO:0009891EFO:0002429
neuroblastoma1MONDO:0005072EFO:0000621
primary myelofibrosis1MONDO:0009692MONDO:0044903

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

Clinical trials

Total trials: 11.

Phase distribution

PhaseTrials
PHASE27
PHASE1/PHASE22
PHASE31
PHASE11

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00557193PHASE3COMPLETEDCombination Chemotherapy With or Without Lestaurtinib in Treating Younger Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
NCT00030186PHASE2COMPLETEDOpen Study of CEP-701 in Patients With Refractory Acute Myeloid Leukemia With FLT-3 Mutation
NCT00079482PHASE2COMPLETEDStudy of CEP-701 (Lestaurtinib) in Patients With Acute Myeloid Leukemia (AML)
NCT00081601PHASE2COMPLETEDStudy of CEP-701 in Treatment of Prostate Cancer
NCT00236119PHASE2COMPLETEDStudy of the Efficacy, Safety and Tolerability of Oral CEP-701 in Patients With Severe Psoriasis
NCT00242827PHASE2TERMINATEDEfficacy and Safety of Oral CEP-701 for the Treatment of Patients With Advanced Multiple Myeloma
NCT00469859PHASE1/PHASE2COMPLETEDLestaurtinib, Cytarabine, and Idarubicin in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00494585PHASE2COMPLETEDCEP-701 for PH-negative Myelofibrosis
NCT00586651PHASE2COMPLETEDOpen-Label Study of Oral CEP-701 (Lestaurtinib) in Patients With Polycythemia Vera or Essential Thrombocytosis
NCT00668421PHASE1/PHASE2UNKNOWNCEP-701 (Lestaurtinib) in Myelofibrosis
NCT00084422PHASE1COMPLETEDN2001-03: CEP-701 in Treating Young Patients With Recurrent or Refractory High-Risk Neuroblastoma

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.

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

MoleculeSourceStatusShared targets
AfatinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
AxitinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
BosutinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
CrizotinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
ErlotinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
FedratinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
GefitinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
ImatinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
MIDOSTAURINChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
NeratinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
NilotinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
PazopanibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
QuizartinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
SorafenibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
SUNITINIBChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
VandetanibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1, LATS2
NINTEDANIBChEMBLPhase 4 (approved)FLT3, LATS1, LATS2
DOVITINIBChEMBLPhase 3FLT3, LATS1, LATS2
LINIFANIBChEMBLPhase 3FLT3, LATS1, LATS2
RUBOXISTAURINChEMBLPhase 3FLT3, LATS1, LATS2
SU-014813ChEMBLPhase 2FLT3, LATS1, LATS2
TG100-115ChEMBLPhase 2FLT3, LATS1, LATS2
TOZASERTIBChEMBLPhase 2FLT3, LATS1, LATS2
IdelalisibPubChemApprovedFLT3, LATS1, LATS2
SelumetinibPubChemApprovedFLT3, LATS1, LATS2
AbemaciclibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
CabozantinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
CeritinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
EntrectinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
FOSTAMATINIBChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
GILTERITINIBChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
IBRUTINIBChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
PacritinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
PalbociclibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
PexidartinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
PonatinibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
REGORAFENIBChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
TivozanibChEMBL + PubChemPhase 4 (approved)FLT3, LATS1
CRENOLANIBChEMBLPhase 3FLT3, LATS1
DEFACTINIBChEMBLPhase 3FLT3, LATS1
LINSITINIBChEMBLPhase 3FLT3, LATS1
ORANTINIBChEMBLPhase 3FLT3, LATS1
AT-9283ChEMBLPhase 2FLT3, LATS1
MILCICLIBChEMBLPhase 2FLT3, LATS1
R-406ChEMBLPhase 2FLT3, LATS2
AcalabrutinibPubChemApprovedLATS1, LATS2
BinimetinibPubChemApprovedFLT3, LATS1
dacomitinibPubChemApprovedFLT3, LATS1
DuvelisibPubChemApprovedLATS1, LATS2
LapatinibPubChemApprovedLATS1, LATS2
RuxolitinibPubChemApprovedLATS1, LATS2
TofacitinibPubChemApprovedLATS1, LATS2
TrametinibPubChemApprovedFLT3, LATS1
CAPIVASERTIBChEMBL + PubChemPhase 4 (approved)LATS1
BRIGATINIBChEMBLPhase 4 (approved)FLT3
DASATINIBChEMBLPhase 4 (approved)FLT3
FILGOTINIBChEMBLPhase 4 (approved)FLT3
INFIGRATINIBChEMBLPhase 4 (approved)FLT3
PRALSETINIBChEMBLPhase 4 (approved)FLT3
ALVOCIDIBChEMBLPhase 3FLT3

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