This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Lestaurtinib
Accession Number
DB06469
Type
Small Molecule
Groups
Investigational
Description
Not Available
Structure
Thumb
Synonyms
Not Available
External IDs
A-154475 / A-154475.0 / CEP-701 / KT-555 / KT-5555 / KT5555 / SP-924 / SP924 / SPM-924
Categories
UNII
DO989GC5D1
CAS number
111358-88-4
Weight
Average: 439.471
Monoisotopic: 439.153206168
Chemical Formula
C26H21N3O4
InChI Key
UIARLYUEJFELEN-DMVVYWCZSA-N
InChI
InChI=1S/C26H21N3O4/c1-25-26(32,12-30)10-18(33-25)28-16-8-4-2-6-13(16)20-21-15(11-27-24(21)31)19-14-7-3-5-9-17(14)29(25)23(19)22(20)28/h2-9,18,30,32H,10-12H2,1H3,(H,27,31)/t18?,25-,26-/m0/s1
IUPAC Name
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.1^{15,18}.0^{2,6}.0^{7,27}.0^{8,13}.0^{19,26}.0^{20,25}]octacosa-1(26),2(6),7(27),8,10,12,20(25),21,23-nonaen-3-one
SMILES
C[C@]12O[C@H](C[C@]1(O)CO)N1C3=C(C=CC=C3)C3=C1C1=C(C4=C3C(=O)NC4)C3=CC=CC=C3N21

Pharmacology

Indication

Investigated for use/treatment in pancreatic cancer, prostate cancer, and leukemia (myeloid).

Pharmacodynamics
Not Available
Mechanism of action

Lestaurtinib inhibits autophosphorylation of FMS-like tyrosine kinase 3 (FLT3), resulting in inhibition of FLT3 activity and induction of apoptosis in tumor cells that overexpress FLT3.

TargetActionsOrganism
UReceptor-type tyrosine-protein kinase FLT3Not AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Lestaurtinib.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Lestaurtinib.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Lestaurtinib.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Lestaurtinib.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Lestaurtinib.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Lestaurtinib.
7-ethyl-10-hydroxycamptothecinThe metabolism of 7-ethyl-10-hydroxycamptothecin can be decreased when combined with Lestaurtinib.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Lestaurtinib.
AbaloparatideThe therapeutic efficacy of Abaloparatide can be decreased when used in combination with Lestaurtinib.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Lestaurtinib.
Food Interactions
Not Available

References

General References
Not Available
External Links
ChemSpider
8108517
ChEMBL
CHEMBL175105
Wikipedia
Lestaurtinib

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentNeuroblastomas1
1, 2Active Not RecruitingTreatmentLeukemias1
1, 2Unknown StatusTreatmentAgnogenic Myeloid Metaplasia / Essential Thrombocythemia (ET) / Polycythemia Vera (PV)1
2CompletedTreatmentAgnogenic Myeloid Metaplasia / Leukemias1
2CompletedTreatmentEssential Thrombocythemia (ET) / Polycythemia Vera (PV)1
2CompletedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2CompletedTreatmentMyeloid Leukemias1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentPsoriasis1
2TerminatedTreatmentPlasma Cell Myeloma1
3CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Acute Undifferentiated Leukemia (AUL) / Childhood T Acute Lymphoblastic Leukemia / T-cell Childhood Acute Lymphoblastic Leukemia / Untreated Childhood Acute Lymphoblastic Leukemia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.105 mg/mLALOGPS
logP2.28ALOGPS
logP2.86ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)12.26ChemAxon
pKa (Strongest Basic)-1.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area88.65 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity121.41 m3·mol-1ChemAxon
Polarizability47.08 Å3ChemAxon
Number of Rings8ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as indolocarbazoles. These are polycyclic aromatic compounds containing an indole fused to a carbazole.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Carbazoles
Direct Parent
Indolocarbazoles
Alternative Parents
Pyrrolo[2,3-a]carbazoles / Pyrroloindoles / Isoindolones / Indoles / Benzenoids / Tertiary alcohols / Pyrroles / Oxolanes / Heteroaromatic compounds / Secondary carboxylic acid amides
show 8 more
Substituents
Indolocarbazole / Pyrrolo[2,3-a]carbazole / Pyrroloindole / Isoindolone / Indole / Isoindoline / Isoindole or derivatives / Benzenoid / Heteroaromatic compound / Tertiary alcohol
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells...
Gene Name
FLT3
Uniprot ID
P36888
Uniprot Name
Receptor-type tyrosine-protein kinase FLT3
Molecular Weight
112902.51 Da

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Filppula AM, Neuvonen PJ, Backman JT: In vitro assessment of time-dependent inhibitory effects on CYP2C8 and CYP3A activity by fourteen protein kinase inhibitors. Drug Metab Dispos. 2014 Jul;42(7):1202-9. doi: 10.1124/dmd.114.057695. Epub 2014 Apr 8. [PubMed:24713129]

Drug created on March 19, 2008 10:34 / Updated on November 02, 2018 06:17