Bafetinib

KU812 xenograft is established by subcutaneous injection of KU812 cells into the right flank of Balb/c-nu/nu female mice.

(S)-4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-N-(4-methyl-3-(4-(pyrimidin-5-yl)pyrimidin-2-ylamino)phenyl)-3-(trifluoromethyl)benzamide

0-10 uM

<=20 mg/kg/day

Bafetinib is dissolved in 0.5% methylcellulose.

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. [1] In Bcr-Abl+ leukemia cell lines, Bafetinib induces both caspase-mediated and caspase-independent cell death by blocking the phosphorylation of Bcr-Abl. [2]

72 hours

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.

Bafetinib (INNO-406) Chemical Structure