CAS 1000669-72-6|KW-2449

Introduction：Basic information about CAS 1000669-72-6|KW-2449, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. KW-2449 BiologicalActivity
3. Chemical & Physical Properties
4. Synonyms

Common Name	KW-2449
CAS Number	1000669-72-6	Molecular Weight	332.399
Density	1.3±0.1 g/cm3	Boiling Point	604.1±55.0 °C at 760 mmHg
Molecular Formula	C₂₀H₂₀N₄O	Melting Point	/
MSDS	/	Flash Point	319.1±31.5 °C

Names

Name	[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone
Synonym	More Synonyms

KW-2449 BiologicalActivity

Description	KW-2449 is a multi-targeted kinase inhibitor of FLT3, ABL, ABLT315I and Aurora kinase with IC50s of 6.6, 14, 4 and 48 nM, respectively.
Related Catalog	Signaling Pathways >>Cell Cycle/DNA Damage >>Aurora KinaseSignaling Pathways >>Epigenetics >>Aurora KinaseSignaling Pathways >>Protein Tyrosine Kinase/RTK >>Bcr-AblSignaling Pathways >>Protein Tyrosine Kinase/RTK >>FLT3Research Areas >>Cancer
Target	Abl:4 nM (IC50) ABL-T315I:14 nM (IC50) FGFR1:36 nM (IC50) Aurora A:48 nM (IC50) FLT3/D835Y:1 nM (IC50) FLT3:6.6 nM (IC50) JAK2:150 nM (IC50) SRC:400 nM (IC50) PDFGRα:1700 nM (IC50)
In Vitro	KW-2449 shows growth inhibitory activities against FLT3/ITD-, FLT3/D835Y-, and wt-FLT3/FL-expressing 32D cells, MOLM-13 and MV4;11 with GI50 values of 0.024, 0.046, 0.014, 0.024, and 0.011 μM, respectively. KW-2449 suppresses the phosphorylations of FLT3 (P-FLT3) and its downstream molecule phospho-STAT5 (P-STAT5) in MOLM-13 cells in a dose-dependent manner. KW-2449 increases the percentage of cells in the G1 phase of the cell cycle and reciprocally reduced the percentage of cells in the S phase, resulting in the increase of apoptotic cell population[1].
In Vivo	Oral administration of KW-2449 shows dose-dependent and significant tumor growth inhibition in FLT3-mutated xenograft model with minimum bone marrow suppression. In FLT3 wild-type human leukemia, it induces the reduction of phosphorylated histone H3, G2/M arrest, and apoptosis. In imatinib-resistant leukemia, KW-2449 contributes to release of the resistance by the simultaneous down-regulation of BCR/ABL and Aurora kinases. Furthermore, the antiproliferative activity of KW-2449 is confirmed in primary samples from AML and imatinib-resistant patients. The inhibitory activity of KW-2449 is not affected by the presence of human plasma protein, such as α1-acid glycoprotein[1].
Cell Assay	Cell viability is determined by the sodium 3′-[1-(phenylaminocarbonyl)-3, 4-tetrazolium]-bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate assay after incubation with or without KW-2449 for 72 hours at 37°C. The number of viable cells is determined using the Cell Proliferation Kit II[1].
Animal Admin	Mice: SCID mice are subcutaneously inoculated with MOLM-13 cells. Five days after inoculation, tumor volume is measured using the Antitumor test system II. The 25 mice with tumors ranging from 90 to 130 mm3 are selected and randomized using the Antitumor test system II. From the day of randomization, vehicle (0.5 wt/vol% MC400) or KW-2449 (2.5, 5.0, 10, and 20 mg/kg) is orally administered to mice twice a day for 14 days. Tumor volume is measured twice a week during the treatment[1].
References	[1]. Shiotsu Y, et al. KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17.

Chemical & Physical Properties

Density	1.3±0.1 g/cm3
Boiling Point	604.1±55.0 °C at 760 mmHg
Molecular Formula	C₂₀H₂₀N₄O
Molecular Weight	332.399
Flash Point	319.1±31.5 °C
Exact Mass	332.163696
PSA	61.02000
LogP	2.07
Vapour Pressure	0.0±1.7 mmHg at 25°C
Index of Refraction	1.723

Synonyms

{4-[(E)-2-(1H-Indazol-3-yl)vinyl]phenyl}(1-piperazinyl)methanone

cc-533

S2158_Selleck

Methanone, [4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-1-piperazinyl-

KW 2449

KW-2449

KW2449

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