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
C[C@]12O[C@H](C[C@]1(O)CO)n3c4ccccc4c5c6C(=O)NCc6c7c8ccccc8n2c7c35
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
Molecular Formula | C26H21N3O4 |
Molecular Weight | 439.4626 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
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 |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3447 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15528978 |
80 mg 2 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
LESTAURTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
12117 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15528978 |
80 mg 2 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LESTAURTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
618 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15528978 |
20 mg 2 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
LESTAURTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
25858 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15528978 |
80 mg 2 times / day multiple, oral dose: 80 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
LESTAURTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
114857 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15528978 |
80 mg 2 times / day steady-state, oral dose: 80 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
LESTAURTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3530 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15528978 |
20 mg 2 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
LESTAURTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/15528978 |
20 mg 2 times / day multiple, oral dose: 20 mg route of administration: Oral experiment type: MULTIPLE co-administered: |
LESTAURTINIB plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
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 |
|
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. | 2010 Nov 24 |
|
Comprehensive analysis of kinase inhibitor selectivity. | 2011 Oct 30 |
|
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 |
|
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:25:49 GMT 2025
by
admin
on
Mon Mar 31 18:25:49 GMT 2025
|
Record UNII |
DO989GC5D1
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Preferred Name | English | ||
|
Official Name | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Code | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Code | English | ||
|
Code | English | ||
|
Code | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Code | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
FDA ORPHAN DRUG |
219406
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
||
|
EU-Orphan Drug |
EU/3/06/389
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
||
|
NCI_THESAURUS |
C1967
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
||
|
FDA ORPHAN DRUG |
289109
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
||
|
NCI_THESAURUS |
C129825
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
8297
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
SUB32265
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
DB06469
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
C119379
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
100000124422
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
DTXSID5046778
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
111358-88-4
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
DO989GC5D1
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
NN-44
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
CHEMBL603469
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
C48402
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
126565
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY | |||
|
LESTAURTINIB
Created by
admin on Mon Mar 31 18:25:49 GMT 2025 , Edited by admin on Mon Mar 31 18:25:49 GMT 2025
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
TARGET -> INHIBITOR |
|
||
|
TARGET -> INHIBITOR | |||
|
TARGET -> INHIBITOR |
|
||
|
TARGET -> INHIBITOR |
|
||
|
TARGET -> INHIBITOR |
|
||
|
TARGET -> INHIBITOR |
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |
|