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

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

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 8504	4.0 nM [IC50]
Tyrosine-protein kinase receptor FLT3 42 Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22037378	Inhibitor 8504	5.0 nM [IC50]
Tyrosine-protein kinase JAK2 59 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17984313	Inhibitor 8504	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 665	Unknown Approved Use Unknown
Acute myeloid leukemia 141 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21082990 https://www.ncbi.nlm.nih.gov/pubmed/20141349	Primary	Phase II 1147	Unknown Approved Use Unknown
Myelofibrosis 15 Sources: https://clinicaltrials.gov/ct2/show/NCT00494585	Primary	Phase II 1147	Unknown Approved Use Unknown
Polycythemia vera 18 Sources: https://clinicaltrials.gov/ct2/show/NCT00586651	Primary	Phase II 1147	Unknown Approved Use Unknown
Thrombocytosis 1 Sources: https://clinicaltrials.gov/ct2/show/NCT00586651	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	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	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

T_1/2

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
inhibitor 2252 inducer 1087 substrate 1946	inhibitor 2438		inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C8 1057 CYP2C19 2057 P-gp 1741 CYP19A1 429 CYP1A2 2153	CYP1A2 1197 CYP2B6 776

Drug as perpetrator

Target	Modality	Activity
CYP3A4 2633	inducer 1966 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346984#sid=144206186	no
CYP19A1 430	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/743083#sid=144206186	yes [IC50 2.1132 uM]
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=144206186	yes [IC50 4.6109 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes [IC50 4.7 uM]
CYP2C8 1117	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes [IC50 9.5 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18217204/	yes
CYP2C19 2141	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18217204/	yes
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/18217204/	yes

Drug as victim

Target	Modality	Activity
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/24713129/	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/20141349/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 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
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/
MedChem Express	HY-50867	https://www.medchemexpress.com/search.html?q=HY-50867&ft=&fa=&fp=
Molcore	MC34361	http://www.molcore.com/CatMC34361.html
Molnova	M10418	https://www.molnova.com/en/serch-list.html?keywords=M10418
MolPort	MolPort-003-848-372	https://www.molport.com/shop/molecule-link/MolPort-003-848-372
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

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 `Mon Mar 31 18:25:49 GMT 2025` Edited by `admin` on `Mon Mar 31 18:25:49 GMT 2025`
Record UNII	DO989GC5D1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

A-154475

Preferred Name

English

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

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