KW-2449

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H20N4O
Molecular Weight	332.399
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C(N1CCNCC1)C2=CC=C(\C=C\C3=NNC4=C3C=CC=C4)C=C2

InChI

InChIKey=YYLKKYCXAOBSRM-JXMROGBWSA-N

InChI=1S/C20H20N4O/c25-20(24-13-11-21-12-14-24)16-8-5-15(6-9-16)7-10-19-17-3-1-2-4-18(17)22-23-19/h1-10,21H,11-14H2,(H,22,23)/b10-7+

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19541823
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19541823

KW-2449, a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase, is under investigation to treat leukaemia patients. KW-2449 is a multikinase inhibitor of FLT3, ABL, ABL-T315I, and Aurora kinase with IC50 values of 6.6nM, 14nM, 4nM and 48nM, respectively. KW-2449 has potent growth inhibitory activity against various types of leukaemia by several mechanisms of action. Kyowa Hakko Kirin Pharma Inc. (a US subsidiary of Kyowa Hakko Kirin Co) was developing KW-2449 for the treatment of acute lymphoblastic leukaemia; acute myeloid leukaemia; chronic myeloid leukaemia; myelodysplastic syndromes, but later these studies were discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Tyrosine-protein kinase receptor FLT3 43 Target ID: CHEMBL1974 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19541823	Inhibitor 8297	6.6 nM [IC50]
Tyrosine-protein kinase ABL 29 Target ID: CHEMBL1862 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19541823	Inhibitor 8297	14.0 nM [IC50]
Fibroblast growth factor receptor 1 45 Target ID: CHEMBL3650 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19541823	Inhibitor 8297	36.0 nM [IC50]
Serine/threonine-protein kinase Aurora-A 37 Target ID: CHEMBL4722 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19541823	Inhibitor 8297	48.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Acute myelogenous leukemia 19 Sources: https://clinicaltrials.gov/ct2/show/NCT00779480 http://adisinsight.springer.com/drugs/800025222	Primary	Phase I 428	Unknown Approved Use Unknown
Myelodysplastic syndromes 58 Sources: https://clinicaltrials.gov/ct2/show/NCT00346632 http://adisinsight.springer.com/drugs/800025222	Primary	Phase I 428	Unknown Approved Use Unknown
Chronic myelogenous leukemia 22 Sources: https://clinicaltrials.gov/ct2/show/NCT00346632 http://adisinsight.springer.com/drugs/800025222	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
180 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28751116	1 mg/kg single, oral dose: 1 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		KW-2449 plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
1190 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28751116	1 mg/kg single, oral dose: 1 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		4-[4-[(E)-2-(1H-INDAZOL-3-YL)ETHENYL]BENZOYL]PIPERAZIN-2-ONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
821 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28751116	1 mg/kg single, oral dose: 1 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		KW-2449 plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
8540 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28751116	1 mg/kg single, oral dose: 1 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		4-[4-[(E)-2-(1H-INDAZOL-3-YL)ETHENYL]BENZOYL]PIPERAZIN-2-ONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.93 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28751116	1 mg/kg single, oral dose: 1 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		KW-2449 plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN
2.65 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/28751116	1 mg/kg single, oral dose: 1 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		4-[4-[(E)-2-(1H-INDAZOL-3-YL)ETHENYL]BENZOYL]PIPERAZIN-2-ONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY107129	https://www.001chemical.com/chem/search?q=DY107129
1PlusChem LLC	1P00019L	https://www.1pchem.com/search?query=1P00019L
AK Scientific	SYN1205	https://aksci.com/item_detail.php?cat=SYN1205
AK Scientific	X7371	https://aksci.com/item_detail.php?cat=X7371
Angene	AGN-PC-0OPDP3	http://www.angenechemical.com/productshow/AGN-PC-0OPDP3.html
AstaTech	H11584	http://astatechinc.com/CPSResult.php?CRNO=H11584
BOC Sciences	1000669-72-6	http://www.bocsci.com/description.asp?cas=1000669-72-6
BioSynth	J-502761	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/J-502761
Chem Scene	CS-0231	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0231
ChemShuttle	113644	https://www.chemshuttle.com/catalogsearch/result/?q=113644
Combi-Blocks	QW-8266	http://www.combi-blocks.com/cgi-bin/find.cgi?QW-8266
Excenen	EX-A2306	http://www.excenen.com/searchresultlist.php?id=EX-A2306
Fluorochem	540095	http://www.fluorochem.co.uk/Products/Product?code=540095
KeyOrganics	AS-16334	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-16334
KeyOrganics	AS-71712	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-71712
Lab Network	LN01343354	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01343354
Matrix Scientific	132741	http://www.matrixscientific.com/132741.html
MedChem Express	HY-10339	https://www.medchemexpress.com/search.html?q=HY-10339&ft=&fa=&fp=
MolPort	MolPort-016-633-288	https://www.molport.com/shop/molecule-link/MolPort-016-633-288
MolPort	MolPort-039-062-175	https://www.molport.com/shop/molecule-link/MolPort-039-062-175
MolPort	MolPort-042-676-013	https://www.molport.com/shop/molecule-link/MolPort-042-676-013
Molcore	MC107129	http://www.molcore.com/CatMC107129.html
Molnova	M10007	https://www.molnova.com/en/serch-list.html?keywords=M10007
MuseChem	I000066	https://www.musechem.com/product/I000066.html
PI Chemicals	PI-39488	http://www.pipharm.com/catalog_products/PI-39488.html
Selleck Chemicals	S2158	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2158
ShangHai Biochempartner	BCP02848	http://www.biochempartner.com/search_BCP02848
eMolecules	259855832	https://orderbb.emolecules.com/search/#?query=259855832
eMolecules	32278200	https://orderbb.emolecules.com/search/#?query=32278200
eMolecules	44841848	https://orderbb.emolecules.com/search/#?query=44841848
eMolecules	50406360	https://orderbb.emolecules.com/search/#?query=50406360
eNovation Chemicals	D491433	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D491433&searchbtn.x=0&searchbtn.y=0
eNovation Chemicals	K31325	https://www.enovationchem.com/Products.asp?SEARCHTEXT=K31325&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-6647948473	https://mcule.com/MCULE-6647948473/
mcule	MCULE-8979781866	https://mcule.com/MCULE-8979781866/
mcule	MCULE-9860015192	https://mcule.com/MCULE-9860015192/

PubMed

Title	Date	PubMed
KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation.	2009 Aug 20	19541823
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

Patents

Sample Use Guides

In Vivo Use Guide

KW-2449 50 mg capsules administered 3 or 4 times per day for 21-day cycles up to 6 cycles

Route of Administration: Oral

In Vitro Use Guide

KW-2449 showed growth inhibitory activities against FLT3/ITD-, FLT3/D835Y-, and wt-FLT3/FL-expressing 32D cells, MOLM-13 and MV4;11 with half-maximal growth inhibitory concentration (GI50) values of 0.024, 0.046, 0.014, 0.024, and 0.011 uM, respectively. KW-2449 (0.60 uM) induced G2/M arrest and apparent increase of sub-G1 apoptotic RS4;11 cells after 24 hours and 48 hours of exposure, respectively.

Name

Type

Language

KW-2449

Common Name

English

(4-((1E)-2-(1H-INDAZOL-3-YL)ETHENYL)PHENYL)-1-PIPERAZINYLMETHANONE

Systematic Name

English

PIPERAZINE, 1-(4-((1E)-2-(1H-INDAZOL-3-YL)ETHENYL)BENZOYL)-

Systematic Name

English

KW 2449 [WHO-DD]

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID701026046