SML3546
KW-2449
≥95% (HPLC)
Synonym(s):
(E)-1-{4-[2-(1H-Indazol-3-yl)vinyl]benzoyl}piperazine, KW 2449, KW2449, [4-[(E)-2-(1H-Indazol-3-yl)ethenyl]phenyl]-1-piperazinylmethanone, [4-[(E)-2-(1H-Indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone
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About This Item
Empirical Formula (Hill Notation):
C20H20N4O
CAS Number:
Molecular Weight:
332.40
NACRES:
NA.77
UNSPSC Code:
12352200
assay
≥95% (HPLC)
form
powder
color
white to beige
solubility
DMSO: 2 mg/mL, clear
storage temp.
2-8°C
Quality Level
Related Categories
Biochem/physiol Actions
Orally active FLT3, ABL, FGFR1, Aurora A inhibitor and a KCC2 expression-enhancing compound (KEEC) with in vivo leukemia & Rett syndrome (RTT) therapeutic efficacy.
KW-2449 is an orally active potent kinase inhibitor against FLT3 (wt/D835Y IC50 = 6.6/1 nM), ABL (wt/T315I IC50 = 14/4 nM), FGFR1 (IC50 = 36 nM), and aurora A (IC50 = 48 nM). KW-2449 also inhibits JAK2, KIT, Src with reduced potency (IC50 = 150, 300, 400 nM, respectively), but not EGFR, Fms, IGF1R or PDGFRα (IC50 >1 μM). In addition to its anti-leukemia efficacy in cultures (GI50 10-650 nM) and in vivo (5-20 mg/kg b.i.d. p.o.), KW-2449 is also a K+/Cl- cotransporter 2 (KCC2) expression-enhancing compound (KEEC) that ameliorates disease phenotypes in a Rett syndrome (RTT) model in Mecp2 mutant mice (2 mg/kg/d i.p.).
Storage Class
11 - Combustible Solids
wgk
WGK 3
flash_point_f
Not applicable
flash_point_c
Not applicable
Regulatory Information
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FLT3-mutant allelic burden and clinical status are predictive of response to FLT3 inhibitors in AML
Blood, 115(7), 1425-1432 (2010)
A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response
Blood, 113(17), 3938-3946 (2009)
HDAC inhibitors potentiate the activity of the BCR/ABL kinase inhibitor KW-2449 in imatinib-sensitive or -resistant BCR/ABL+ leukemia cells in vitro and in viv
Clinical Cancer Research, 17(10), 3219-3232 (2011)
FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivo
Blood, 117(12), 3286-3293 (2011)
KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation
Blood, 114(8), 1607-1617 (2009)
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