LESTAURTINIB

Investigational

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 8228	4.0 nM [IC50]
Tyrosine-protein kinase receptor FLT3 43 Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8228	5.0 nM [IC50]
Tyrosine-protein kinase JAK2 53 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17984313	Inhibitor 8228	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 663	Unknown Approved Use Unknown
Acute myeloid leukemia 135 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21082990 https://www.ncbi.nlm.nih.gov/pubmed/20141349	Primary	Phase II 1144	Unknown Approved Use Unknown
Myelofibrosis 15 Sources: https://clinicaltrials.gov/ct2/show/NCT00494585	Primary	Phase II 1144	Unknown Approved Use Unknown
Polycythemia vera 14 Sources: https://clinicaltrials.gov/ct2/show/NCT00586651	Primary	Phase II 1144	Unknown Approved Use Unknown
Thrombocytosis 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00586651	Primary	Phase II 1144	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579 inducer 768 substrate 1709	inhibitor 1752		inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 901 CYP2C19 1463 P-gp 1437 CYP19A1 58 CYP1A2 1509	CYP1A2 1032 CYP2B6 660

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1909	inducer 1542 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346984#sid=144206186	no
CYP19A1 58	inhibitor 3240 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743083#sid=144206186	yes [IC50 2.1132 uM]
P-gp 1626	inhibitor 3240 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=144206186	yes [IC50 4.6109 uM]
CYP3A4 1909	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes [IC50 4.7 uM]
CYP2C8 955	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes [IC50 9.5 uM]
CYP1A2 1673	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/18217204/	yes
CYP2C19 1537	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/18217204/	yes
CYP2C9 1803	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/18217204/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1032	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes
CYP2B6 660	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes
CYP3A4 1709	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/20141349/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 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
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 `Wed Jul 05 23:47:49 UTC 2023` Edited by `admin` on `Wed Jul 05 23:47:49 UTC 2023`
Record UNII	DO989GC5D1
Record Status	`Validated (UNII)`
Record Version

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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