| Identification | Back Directory | [Name]
[4-[2-(1H-Indazol-3-yl)ethenyl]phenyl]-1-piperazinylmethanone | [CAS]
1000669-72-6 | [Synonyms]
CS-468
KW 2449
KW-2449 100MG
KW2449;KW 2449
KW-2449;KW 2449; KW2449
[4-[2-(1H-Indazol-3-yl)ethenyl]phenyl]-1-piperazinylmethanone
{4-[(E)-2-(1H-Indazol-3-yl)vinyl]phenyl}(1-piperazinyl)methanone
Methanone, [4-[2-(1H-indazol-3-yl)ethenyl]phenyl]-1-piperazinyl-
3-[(E)-2-{4-[(PIPERAZIN-1-YL)CARBONYL]PHENYL}ETHENYL]-2H-INDAZOLE
(E)-(4-(2-(1H-indazol-3-yl)vinyl)phenyl)(piperazin-1-yl)methanone
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone
[4-[2-(1H-Indazol-3-yl)ethenyl]phenyl]-1-piperazinylmethanone USP/EP/BP
KW2449(E)-(4-(2-(1H-indazol-3-yl)vinyl)phenyl)(piperazin-1-yl)methanonehydrochloride | [Molecular Formula]
C20H20N4O | [MDL Number]
MFCD18385006 | [MOL File]
1000669-72-6.mol | [Molecular Weight]
332.41 |
| Chemical Properties | Back Directory | [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. |
| Hazard Information | Back Directory | [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]
Shiotsu et al. (2007) KW-2449, a Novel Multi-Kinase Inhibitor Against FLT3, Abl, FGFR1, and Aurora, Suppresses the Growth of AML Both In Vitro and In Vivo; Blood; 110 1832
Shiotsu et al. (2009) KW-2449, a Novel Multi-Kinase Inhibitor, suppresses the growth of leukemia cells with FLTY3 mutations or T315l-mutated BCR/ABL translocation; Blood; 114 1607
Pratz et al. (2009) A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response; Blood; 113 3938 |
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