Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C26H21N3O4 |
Molecular Weight | 439.4626 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@]12C[C@](O)(CO)[C@](C)(O1)N3C4=C(C=CC=C4)C5=C3C6=C(C7=C(C=CC=C7)N26)C8=C5CNC8=O
InChI
InChIKey=UIARLYUEJFELEN-LROUJFHJSA-N
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+/m1/s1
Lestaurtinib (CEP-701, KT-5555) is an orally bio-available polyaromatic indolocarbazole
alkaloid derived from K-252a. Lestaurtinib is a multi-targeted tyrosine kinase inhibitor which has been shown to potently inhibit FLT3 at nanomolar concentrations in preclinical studies, leading to its rapid development as a potential targeted agent for treatment of AML. Phase I studies have shown lestaturtinib to be an active agent particularly when used in combination with cytotoxic drugs. Currently, Phase II and Phase III studies are underway aiming to establish the future of this agent as a treatment option for patients with FLT3-ITD AML.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
4.0 nM [IC50] | |||
Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378 |
5.0 nM [IC50] | ||
Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17984313 |
1.0 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator​
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
yes [IC50 2.1132 uM] | ||||
yes [IC50 4.6109 uM] | ||||
yes [IC50 4.7 uM] | ||||
yes [IC50 9.5 uM] | ||||
yes | ||||
yes | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo. | 2002 Jun 1 |
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Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. | 2010 Nov 24 |
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Comprehensive analysis of kinase inhibitor selectivity. | 2011 Oct 30 |
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Development of a novel azaspirane that targets the Janus kinase-signal transducer and activator of transcription (STAT) pathway in hepatocellular carcinoma in vitro and in vivo. | 2014 Dec 5 |
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Drug repurposing screen identifies lestaurtinib amplifies the ability of the poly (ADP-ribose) polymerase 1 inhibitor AG14361 to kill breast cancer associated gene-1 mutant and wild type breast cancer cells. | 2014 Jun 24 |
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00079482
Induction chemotherapy with or without sequential treatment with oral Lestaurtinib (CEP-701) at 80 mg bid. For patients with duration of first CR of 1 to 6 months, the induction regimen will be MEC.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16857987
Lestaurtinib (CEP-701) potently inhibits FLT3/ITD autophosphorylation with a half maximal inhibitory concentration (IC50) of approximately 2 nM. Inhibition of FLT3 to 15% of its baseline level of autophosphorylation (the level of inhibition required to induce a significant cytotoxic effect on FLT3-dependent cell lines) occurs at a concentration of roughly 5 uM.
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
219406
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EU-Orphan Drug |
EU/3/06/389
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NCI_THESAURUS |
C1967
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FDA ORPHAN DRUG |
289109
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NCI_THESAURUS |
C129825
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8297
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SUB32265
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DB06469
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C119379
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100000124422
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DTXSID5046778
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111358-88-4
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DO989GC5D1
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NN-44
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CHEMBL603469
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C48402
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126565
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LESTAURTINIB
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ACTIVE MOIETY