ChemicalBook Product Catalog Biochemical Engineering Inhibitors Angiogenesis FLT3 inhibitors [4-[2-(1H-Indazol-3-yl)ethenyl]phenyl]-1-piperazinylmethanone

[4-[2-(1H-Indazol-3-yl)ethenyl]phenyl]-1-piperazinylmethanone

Product Name[4-[2-(1H-Indazol-3-yl)ethenyl]phenyl]-1-piperazinylmethanone
CAS1000669-72-6
MFC20H20N4O
MW332.4
EINECS
MOL File1000669-72-6.mol

Chemical Properties

Boiling point	604.1±55.0 °C(Predicted)
Density	1.28
storage temp.	-20°C
solubility	Soluble in DMSO (>25 mg/ml)
form	solid
pka	13.76±0.40(Predicted)
color	Pale yellow
Stability	Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.

Usage And Synthesis

Description

KW-2449 is a potent multikinase inhibitor (IC50’s: FLT3 = 7 nM, FGFR1 = 36 nM, Abl = 14 nM, Abl-T315 = 4 nM) with anti-leukemic effects.1,2,3

Uses

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.

Definition

ChEBI: [4-[2-(1H-indazol-3-yl)ethenyl]phenyl]-(1-piperazinyl)methanone is a member of indazoles.

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].

target

FLT3

IC 50

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)

References

[1] Y. SHIOTSU. KW-2449, a Novel Multi-Kinase Inhibitor Against FLT3, Abl, FGFR1 and Aurora, Suppresses the Growth of AML Both In Vitro and In Vivo .[J]. Blood, 2007, 110 1: 1832-1832. DOI:10.1182/blood.v110.11.1832.1832
[2] KW-2449, a Novel Multi-Kinase Inhibitor, suppresses the growth of leukemia cells with FLTY3 mutations or T315l-mutated BCR/ABL translocation
[3] KEITH W PRATZ. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response.[J]. Blood, 2009, 113 17: 3938-3946. DOI:10.1182/blood-2008-09-177030

[4-[2-(1H-Indazol-3-yl)ethenyl]phenyl]-1-piperazinylmethanone Supplier

[4-[2-(1H-Indazol-3-yl)ethenyl]phenyl]-1-piperazinylmethanone manufacturers

Related Product Information

Send Inquriy