Item no. |
S1369-50 |
Manufacturer |
Selleckchem
|
CASRN |
859212-16-1 |
Amount |
50 mg |
Category |
|
Type |
Inhibitors |
Specific against |
other |
ECLASS 10.1 |
32160490 |
ECLASS 11.0 |
32160490 |
UNSPSC |
12000000 |
Alias |
NS-187 |
Similar products |
Bafetinib |
Available |
|
Administration |
Administered via p.o. |
Animal Models |
KU812 xenograft is established by subcutaneous injection of KU812 cells into the right flank of Balb/c-nu/nu female mice. |
Cell lines |
K562, BaF3/wt, BaF3/E255K, and BaF3/T315I cells |
Chemical Name |
(S)-4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-N-(4-methyl-3-(4-(pyrimidin-5-yl)pyrimidin-2-ylamino)phenyl)-3-(trifluoromethyl)benzamide |
Clinical Trials |
Bafetinib is currently in Phase II clinical trials in patients with hormone refractory prostate cancer. |
Concentrations |
0-10 uM |
Description |
Bafetinib (INNO-406) is a potent and selective dual Bcr-Abl/Lyn inhibitor with IC50 of 5.8 nM and 19 nM, respectively. |
Dosages |
<=20 mg/kg/day |
Features |
Dual Bcr-Abl/Lyn inhibitor |
Formulation |
Bafetinib is dissolved in 0.5% methylcellulose. |
IC50 |
5.8 nM, 5.8 nM, 5.8 nM, 5.8 nM, 5.8 nM, 5.8 nM |
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. [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] |
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%. [1] 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. [3] |
Incubation Time |
72 hours |
Kinase Assay |
Kinase assay, Bcr-Abl kinase assays are performed in 25 uL of reaction mixture containing 250 uM peptide substrate, 740 Bq/uL [gamma-33P]ATP, and 20 uM cold adenosine triphosphate (ATP) by using the SignaTECT protein tyrosine kinase assay system. Each Bcr-Abl kinase is used at a concentration of 10 nM. Kinase assays for Abl, Src, and Lyn are carried out with an enzyme-linked immunosorbent assay (ELISA) kit. The inhibitory effects of NS-187 against 79 tyrosine kinases are tested with KinaseProfiler. |
Method |
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. |
Molecular Weight (MW) |
576, 62 |
Picture ChemicalStructure Description |
Bafetinib (INNO-406) Chemical Structure |
Storage |
2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO |
Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.
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