Bafetinib

SKU: orb1300879

Description

Bafetinib (INNO-406) is a potent and selective dual inhibitor of Bcr-Abl and Lyn kinases, with IC50 values of 5.8 nM and 19 nM, respectively. It shows minimal activity against c-Kit and PDGFR and is ineffective against the T315I mutant. This compound is used in research for chronic myeloid leukemia, demonstrating efficacy in both cellular and animal models of the disease.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 859212-16-1
• MW: 576.62
• Purity: 99.68% (May vary between batches)
• Formula: C₃₀H₃₁F₃N₈O
• SMILES: CN(C)[C@H]1CCN(Cc2ccc(cc2C(F)(F)F)C(=O)Nc2ccc(C)c(Nc3nccc(n3)-c3cncnc3)c2)C1
• Target: Src,Bcr-Abl,Apoptosis,Autophagy
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (5.72 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:120 mg/mL (208.11 mM);Ethanol:< 1 mg/mL (insoluble or slightly soluble)

Bioactivity

• Target IC50:
  Lyn:19 nM|Abl:5.8 nM
• In Vivo:
  In Bcr-Abl–positive KU812 mouse model, Bafetinib (0.2 mg/kg/day) significantly inhibits tumor growth, and completely inhibits tumor growth without adverse effects at 20 mg/kg/day. For Balb/c mice, Bafetinib shows maximal tolerated dose of 200 mg/kg/d and bioavailability value (BA) of 32%. In a Central nervous system (CNS) leukemia model bearing Ba/F3/wt bcr-ablGFP, Ba/F3/Q252H, or Ba/F3/M351T cells, combination treatment of Bafetinib (60 mg/kg) and cyclosporine A (CsA) (50 mg/kg) leads to more significant inhibition of leukemia growth in the brain than either Bafetinib or CsA alone.
• In Vitro:
  Bafetinib blocks WT Bcr-Abl autophosphorylation and its downstream kinase activity with IC50 of 11 nM and 22 nM in K562 and 293T cells, respectively. Bafetinib suppresses the growth of the Bcr-Abl-positive cell lines including K562, KU812, and BaF3/wt cells potently without effects on the proliferation of the Bcr-Abl-negative U937 cell line. Moreover, Bafetinib exhibits a dose-dependent antiproliferative effect against Bcr-Abl point mutant cell lines, such as BaF3/E255K cells. In Bcr-Abl+ leukemia cell lines, Bafetinib induces both caspase-mediated and caspase-independent cell death by blocking the phosphorylation of Bcr-Abl.
• Cell Research:
  K562, BaF3/wt, BaF3/E255K, and BaF3/T315I cells are plated at 1 × 103 in 96-well plates, whereas KU812 and U937 cells are plated at 5 × 103 in 96-well plates. Cells are incubated with serial dilutions of Bafetinib for 3 days. Cell proliferation is measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Nacalai Tesque) assay, and the 50% inhibitory concentration (IC50) values are calculated by fitting the data to a logistic curve. (Only for Reference)

Storage & Handling

• Storage: store at low temperature,keep away from moisture | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

INNO 406, INNO406, INNO-406, Inhibitor, NS187, NS-187, NS 187, inhibit, mutations, Lyn, Abl, Autophagy, Apoptosis, Bafetinib, BcrAbl, Bcr-Abl, philadelphia chromosome-positive leukemias, Src

Compound Identifiers

PubChem CID

11387605