LESTAURTINIB

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

Structure Search

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

HIDE SMILES / InChI

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21082990 | https://www.ncbi.nlm.nih.gov/pubmed/20141349

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	Potency
Nerve growth factor receptor Trk-A 15 Target ID: CHEMBL2815 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20141349 \| https://www.ncbi.nlm.nih.gov/pubmed/23243060 \| https://www.ncbi.nlm.nih.gov/pubmed/11489797	Inhibitor 8297	4.0 nM [IC50]
Tyrosine-protein kinase receptor FLT3 43 Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8297	5.0 nM [IC50]
Tyrosine-protein kinase JAK2 55 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17984313	Inhibitor 8297	1.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Acute lymphoblastic leukemia 27 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21082990 https://www.ncbi.nlm.nih.gov/pubmed/20141349	Primary	Phase III 656	Unknown Approved Use Unknown
Acute myeloid leukemia 136 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21082990 https://www.ncbi.nlm.nih.gov/pubmed/20141349	Primary	Phase II 1132	Unknown Approved Use Unknown
Myelofibrosis 15 Sources: https://clinicaltrials.gov/ct2/show/NCT00494585	Primary	Phase II 1132	Unknown Approved Use Unknown
Polycythemia vera 15 Sources: https://clinicaltrials.gov/ct2/show/NCT00586651	Primary	Phase II 1132	Unknown Approved Use Unknown
Thrombocytosis 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00586651	Primary	Phase II 1132	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 inducer 781 substrate 1737	inhibitor 1767		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 911 CYP2C19 1478 P-gp 1461 CYP19A1 60 CYP1A2 1524	CYP1A2 1054 CYP2B6 664

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inducer 1573 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346984#sid=144206186	no
CYP19A1 60	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743083#sid=144206186	yes [IC50 2.1132 uM]
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=144206186	yes [IC50 4.6109 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes [IC50 4.7 uM]
CYP2C8 965	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes [IC50 9.5 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18217204/	yes
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18217204/	yes
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/18217204/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes
CYP2B6 664	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20141349/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=144206186

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34361	https://www.001chemical.com/chem/search?q=DY34361
1PlusChem LLC	1P007BEN	https://www.1pchem.com/search?query=1P007BEN
AK Scientific	V0246	https://aksci.com/item_detail.php?cat=V0246
Angene	AGN-PC-0P1XS4	http://www.angenechemical.com/productshow/AGN-PC-0P1XS4.html
ApexBio Technology	A4513	https://www.apexbt.com/catalogsearch/result/?q=A4513
Apollo Scientific	BIL2000	http://www.apolloscientific.co.uk/chemical_results.php?qstext=BIL2000&product_group=%25&search_fieldname=header_search
BOC Sciences	111358-88-4	http://www.bocsci.com/description.asp?cas=111358-88-4
Cayman Chemical	12094	http://www.caymanchem.com/app/template/Product.vm/catalog/12094
Chem Scene	CS-0004336	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0004336
MedChem Express	HY-50867	https://www.medchemexpress.com/search.html?q=HY-50867&ft=&fa=&fp=
MolPort	MolPort-003-848-372	https://www.molport.com/shop/molecule-link/MolPort-003-848-372
Molcore	MC34361	http://www.molcore.com/CatMC34361.html
Molnova	M10418	https://www.molnova.com/en/serch-list.html?keywords=M10418
ShangHai Biochempartner	BCP06977	http://www.biochempartner.com/search_BCP06977
Tocris	3395	https://www.tocris.com/search.php?Type=QuickSearch&Value=3395
Toronto Research Chemicals	A133110	https://www.trc-canada.com/product-detail/?CatNum=A133110
Toronto Research Chemicals	L329800	https://www.trc-canada.com/product-detail/?CatNum=L329800
eMolecules	10484307	https://orderbb.emolecules.com/search/#?query=10484307
eMolecules	300472873	https://orderbb.emolecules.com/search/#?query=300472873
mcule	MCULE-7208220282	https://mcule.com/MCULE-7208220282/

PubMed

Title	Date	PubMed
A FLT3-targeted tyrosine kinase inhibitor is cytotoxic to leukemia cells in vitro and in vivo.	2002 Jun 1	12010785
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.	2010 Nov 24	21095574
Comprehensive analysis of kinase inhibitor selectivity.	2011 Oct 30	22037378
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	25320076
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	24962108

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Fri Dec 15 16:21:13 GMT 2023` Edited by `admin` on `Fri Dec 15 16:21:13 GMT 2023`
Record UNII	DO989GC5D1
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

LESTAURTINIB

Official Name

English

LESTAURTINIB [MART.]

Common Name

English

SP924

Code

English

CEP-701

Code

English

KT-555

Code

English

A-154475.0

Code

English

lestaurtinib [INN]

Common Name

English

KT-5555

Code

English

A-154475

Code

English

SP-924

Code

English

SPM-924

Code

English

LESTAURTINIB [USAN]

Common Name

English

Lestaurtinib [WHO-DD]

Common Name

English

KT5555

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

219406

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

EU-Orphan Drug

EU/3/06/389

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

NCI_THESAURUS

C1967

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

FDA ORPHAN DRUG

289109

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

NCI_THESAURUS

C129825

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

Code System Code Type Description

INN

8297

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

PRIMARY

EVMPD

SUB32265

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

PRIMARY

DRUG BANK

DB06469

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

PRIMARY

MESH

C119379

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

PRIMARY

SMS_ID

100000124422

Created by admin on Fri Dec 15 16:21:14 GMT 2023 , Edited by admin on Fri Dec 15 16:21:14 GMT 2023

PRIMARY

EPA CompTox

DTXSID5046778

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

PRIMARY

CAS

111358-88-4

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

PRIMARY

FDA UNII

DO989GC5D1

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

PRIMARY

USAN

NN-44

Created by admin on Fri Dec 15 16:21:14 GMT 2023 , Edited by admin on Fri Dec 15 16:21:14 GMT 2023

PRIMARY

ChEMBL

CHEMBL603469

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

PRIMARY

NCI_THESAURUS

C48402

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

PRIMARY

PUBCHEM

126565

Created by admin on Fri Dec 15 16:21:13 GMT 2023 , Edited by admin on Fri Dec 15 16:21:13 GMT 2023

PRIMARY

WIKIPEDIA

LESTAURTINIB

Created by admin on Fri Dec 15 16:21:14 GMT 2023 , Edited by admin on Fri Dec 15 16:21:14 GMT 2023

PRIMARY

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Related Record Type Details


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LESTAURTINIB

ACTIVE MOIETY

Amount:

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/21082990 | https://www.ncbi.nlm.nih.gov/pubmed/20141349

Originator

Approval Year

Targets

Conditions

Approved Use

Approved Use

Approved Use

Approved Use

Approved Use

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/21082990 | https://www.ncbi.nlm.nih.gov/pubmed/20141349

Drug as perpetrator