B1011-5mg | Bafetinib (INNO-406) [887650-05-7] Clinisciences

Background

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.

Product Citation

1. Gabriella R. Sterne. "Signaling mechanisms of Down syndrome cell adhesion molecule in presynaptic arbor size control." University of Michigan.2016.
2. 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

Chemical Properties

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.

Protocol

Kinase experiment [1]:
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]:
Cell lines	K562, BaF3/wt and KU812 cell lines
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.
Reacting condition	0-10 μM for 3 days
Applications	Bafetinib could suppress the growth of the Bcr-Abl–positive cell lines K562, KU812, and BaF3/wt.
Animal experiment [1]:
Animal models	Bcr-Abl–positive KU812 mouse model
Dosage form	0.2 mg/kg/d and 20 mg/kg/d orally twice a day for 26 consecutive days
Application	Bafetinib suppressed the growth of Bcr-Abl–bearing tumors (KU812) and markedly extends the survival of mice bearing such tumors.
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.
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.

Biological Activity

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