Bafetinib (INNO-406)
Bafetinib is a potent and selective dual inhibitor of Bcr-Abl/Lyn tyrosine kinase with IC50 values of 5.8nM and 19nM, respectively [1].
Bafetinib is a specific dual Abl-Lyn inhibitor. For 79 other tyrosine kinases, 0.1μM bafetinib can inhibit 4 of these enzymes including Abl, Abl-related gene, Fyn and Lyn. Bafetinib can block the autophosphorylation of Bcr-Abl. In K562 and 293T cells transfected with wt Bcr-Abl, bafetinib shows inhibition with IC50 values of 11nM and 22nM, respectively. In the in vitro kinase assays, bafetinib shows inhibition of a variety of Abl kinase mutants such as M244V, G250E, Y253F and F317L. It has no effect on T315I in vitro. Bafetinib also suppresses the growth of Bcr-Abl–positive leukemic cell lines including K562, KU812 and BaF3/wt. The BaF3/E255K cells are also sensitive towards bafetinib. Moreover, bafetinib is highly potent to inhibit tumor growth in murine tumor models [1].
References:
[1] Kimura S, Naito H, Segawa H, et al. NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia. Blood, 2005, 106(12): 3948-3954.
- 1. Hua Cai, Siyu Chen, et al. "Interleukin-22 receptor 1-mediated stimulation of T-type Ca2+ channels enhances sensory neuronal excitability through the tyrosine-protein kinase Lyn-dependent." Cell Commun Signal. 2024 Jun 3;22(1):307. PMID: 38831315
- 2. Gabriella R. Sterne. "Signaling mechanisms of Down syndrome cell adhesion molecule in presynaptic arbor size control." University of Michigan.2016.
- 3. Sterne, Gabriella R., Jung Hwan Kim, and Bing Ye. "Dysregulated Dscam levels act through Abelson tyrosine kinase to enlarge presynaptic arbors." eLife 4 (2015): e05196. PMID:25988807
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 576.62 |
| Cas No. | 887650-05-7 |
| Formula | C30H31F3N8O |
| Solubility | ≥57.7 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O |
| Chemical Name | 4-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-N-[4-methyl-3-[(5-pyrimidin-5-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide |
| SDF | Download SDF |
| Canonical SMILES | CC1=C(C=C(C=C1)NC(=O)C2=CC(=C(C=C2)CN3CCC(C3)N(C)C)C(F)(F)F)NC4=NC=C(C=N4)C5=CN=CN=C5 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Kinase experiment [1]: | |
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Kinase assays |
Bcr-Abl kinase assays were performed in 25 μL of reaction mixture containing 250 μM peptide substrate, 740 Bq/μL [γ-33P]ATP, and 20 μM cold adenosine triphosphate (ATP) by using the SignaTECT protein tyrosine kinase assay system. Each Bcr-Abl kinase was used at a concentration of 10 nM. Kinase assays for Abl, Src, and Lyn were carried out with an enzyme-linked immunosorbent assay (ELISA) kit from Carna Biosciences. |
| Cell experiment [1]: | |
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Cell lines |
K562, BaF3/wt and KU812 cell lines |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
0-10 μM for 3 days |
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Applications |
Bafetinib could suppress the growth of the Bcr-Abl–positive cell lines K562, KU812, and BaF3/wt. |
| Animal experiment [1]: | |
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Animal models |
Bcr-Abl–positive KU812 mouse model |
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Dosage form |
0.2 mg/kg/d and 20 mg/kg/d orally twice a day for 26 consecutive days |
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Application |
Bafetinib suppressed the growth of Bcr-Abl–bearing tumors (KU812) and markedly extends the survival of mice bearing such tumors. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Kimura S, Naito H, Segawa H, et al. NS-187, a potent and selective dual Bcr-Abl/Lyn tyrosine kinase inhibitor, is a novel agent for imatinib-resistant leukemia. Blood, 2005, 106(12): 3948-3954. |
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| Description | Bafetinib (INNO-406) is an orally bioavailable, dual inhibitor of Bcr-Abl and Lyn-kinase with IC50 value of 5.8 nM/19 nM, respectively. | |||||
| Targets | Abl | Lyn | ||||
| IC50 | 5.8 nM | 19 nM | ||||
Quality Control & MSDS
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Chemical structure
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