KW-2449

SKU: orb1704022

Description

KW-2449

Research Area

Cardiovascular Research, Cell Biology, Epigenetics & Chromatin, Signal Transduction, Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1000669-72-6
• MW: 332.4
• Purity: 99.89%
• Formula: C₂₀H₂₀N₄O
• SMILES: O=C(N1CCNCC1)c1ccc(C=Cc2n[nH]c3ccccc23)cc1
• Target: Aurora Kinase,Bcr-Abl,JAK,FLT,c-Kit,Apoptosis,FGFR,Src
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:55 mg/mL (165.46 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (6.02 mM);Ethanol:62 mg/mL (186.52 mM)

Bioactivity

• Target IC50:
  Abl (T315I):14 nM|FLT3 (D835Y):1 nM|Abl:4 nM|Aurora A:48 nM|SRC:400 nM|FGFR1:36 nM|JAK2:150 nM|FLT3:6.6 nM|PDGFRα:1700 nM
• In Vivo:
  In patients with leukemia harboring FLT3 mutations and resistant to Imatinib, KW-2449 exhibits significant activity and has been granted clinical study authorization. KW-2449 reduce the phosphorylation of FLT3 and STAT5 in a dose-dependent manner and shows potent Inhibition against ABL-T315I IC50 4 nM) without affecting PDGFRβ, IGF-1R, EGFR, and several serine/threonine kinases at 1 μM. It significantly inhibit the growth of leukemia cells expressing FLT3/ITD, cells with FLT3/KDM activation, and those overexpressing wild-type FLT3. In MOLM-13 cells, KW-2449 dose-dependently inhibit the phosphorylation of FLT3 an the downstream molecule phospho-STAT5, increase the percentage of cells in the G1 phase, decrease the S phase percentage, leading to an increase in apoptotic cell numbers. KW-2449 promotes dephosphorylation of constitutionally active WT-FLT3 kinase without affecting leukemia cell proliferation. It is rapidly absorbed and converted into a major metabolite M1.
• In Vitro:
  I the MOLM-13 xenograft model, KW-2449 administered orally for 14 days (p.o., 14 days) demonstrates a significant anticancer effect, which exhibits dose-dependency.
• Cell Research:
  Cell viability is determined b 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℃he number of viable cells is determined usin the Cell Proliferation Kit II. For cell-cycle analysis, MOLM-13 and RS4;11 cells are treated with KW-2449. After 24, 48, and 72 hours of incubation at 37℃, DNA contents are analyzed. Cell cycle distribution of K562, TCC-Y, and TCC/Ysr is analyzed 24 hours after treatment with KW-2449 or imatinib. (Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

Src, Abl, Abl (T315I), Apoptosis, AuroraKinase, Aurora A, Aurora Kinase, BcrAbl, Bcr-Abl, cKit, Cluster of differentiation antigen 135, CD135, JAK2, inhibit, KW 2449, KW2449, KW-2449, Kit, FLT3 (D835Y), FLT3, Fms like tyrosine kinase 3, FGFR, FGFR1, Fibroblast growth factor receptor, Inhibitor

Compound Identifiers

PubChem CID

67089852