Bafetinib (INNO-406)

Name: Bafetinib (INNO-406)
Brand: Selleck Chemicals
SKU: S1369
Rating: 5 (14 reviews)

For research use only.

Catalog No.S1369 Synonyms: NS-187

14 publications

CAS No. 859212-16-1

Bafetinib (INNO-406, NS-187) is a potent and selective dual Bcr-Abl/Lyn inhibitor with IC50 of 5.8 nM/19 nM in cell-free assays, does not inhibit the phosphorylation of the T315I mutant and is less potent to PDGFR and c-Kit. Phase 2.

Selleck's Bafetinib (INNO-406) has been cited by 14 publications

Cancer Cell, 2021, 39(3):380-393.e8

PubMed: 33689703 ( click the link to review the publication )

Cell, 2020, 182(3):685-712.e19

PubMed: 32645325 ( click the link to review the publication )

Hum Cell, 2020, 33(4):1112-1119

PubMed: 32862368 ( click the link to review the publication )

Hum Cell, 2020, 10.1007/s13577-020-00420-z

PubMed: 32870449 ( click the link to review the publication )

Drugs R D, 2019, 19(2):149-166

PubMed: 30919310 ( click the link to review the publication )

PLoS One, 2016, 11(10):e0164895

PubMed: 27768734 ( click the link to review the publication )

J Immunol, 2016, 197(5):1587-96

PubMed: 27456487 ( click the link to review the publication )

Sci Rep, 2016, 10.1038/srep25694

PubMed: 27157787 ( click the link to review the publication )

J Med Chem, 2015, 58(1):466-79

PubMed: 25478866 ( click the link to review the publication )

J Med Chem, 2015,

PubMed: ( click the link to review the publication )

Exp Hematol, 2015, 10.1016/j.exphem.2015.11.009

PubMed: 26703895 ( click the link to review the publication )

Oncotarget, 2015, 6(39):42130-49

PubMed: 26517523 ( click the link to review the publication )

Oncotarget, 2015, 6(11):9476-87

PubMed: 25823815 ( click the link to review the publication )

Int Arch Allergy Immunol, 2012, 159(1):15-22

PubMed: 22555087 ( click the link to review the publication )

1 Customer Review

(A) The effect of bafetinib at 3 μM on the expression levels of ABCB1 in SW620/Ad300 cells for 24, 48 and 72 h. (B) The effect of bafetinib at 3 μM on the expression level of ABCG2 in NCI-H460/MX20 cells for 24, 48 and 72 h. Equal amounts of total cell lysate were used for each sample. The effect of bafetinib at 3 μM on the subcellular localization of ABCB1 in ABCB1-overexpressing (C) SW620/Ad300 cells and (D) HEK/ABCB1 cells for 24, 48 and 72 h. The effect of bafetinib at 3 μM on the subcellular localization of ABCG2 in ABCG2-overexpressing (E) NCI-H460/MX20 cells and (F) HEK/ABCG2-R482 cells. Scale bar, 10 μm. PI (propidium Iodide, red) counterstains the nuclei.

Scientific Reports, 2016, 6:25694.. Bafetinib (INNO-406) purchased from Selleck.

Purity & Quality Control

Choose Selective Bcr-Abl Inhibitors

Biological Activity

Description

Features

Dual Bcr-Abl/Lyn inhibitor.

Targets

Abl ^[1] (Cell-free assay)	Lyn ^[1] (Cell-free assay)
5.8 nM	19 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]

Protocol

Kinase Assay:^[1]	- Collapse Kinase assay : Bcr-Abl kinase assays are 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 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.
Cell Research:^[1]	- Collapse Cell lines: K562, BaF3/wt, BaF3/E255K, and BaF3/T315I cells Concentrations: 0-10 μM Incubation Time: 72 hours 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. (Only for Reference)
Animal Research:^[1]	- Collapse Animal Models: KU812 xenograft is established by subcutaneous injection of KU812 cells into the right flank of Balb/c-nu/nu female mice. Dosages: ≤20 mg/kg/day Administration: Administered via p.o. (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	100 mg/mL (173.42 mM)
	Water	Insoluble
	Ethanol	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 0.5% methylcellulose+0.2% Tween 80 For best results, use promptly after mixing.	30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information Download Bafetinib (INNO-406) SDF Download Bafetinib (INNO-406) SDF

Molecular Weight	576.62
Formula	C₃₀H₃₁F₃N₈O
CAS No.	859212-16-1
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	NS-187
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=CC(=N4)C5=CN=CN=C5

In vivo Formulation Calculator (Clear solution)

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take μL DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
2.Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.

Bio Calculators

Molarity Calculator

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This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

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The Serial Dilution Calculator Equation

Serial Dilutions
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Computed Result

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
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C8=C7/X	C8:	LOG(C8):

Molecular Weight Calculator

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Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

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Molarity Calculator

Clinical Trial Information (data from https://clinicaltrials.gov, updated on 2021-05-17)

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00352677	Completed	Drug: INNO-406	Chronic Myeloid Leukemia\|Acute Lymphocytic Leukemia	CytRx	July 2006	Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

Frequently Asked Questions

Question 1:
Can you suggest the route of in vivo administration for S1369?
Answer:
S1369 in 0.5% methylcellulose+0.2% Tween 80 at 30mg/ml is a suspension, and it is fine for oral gavage. If you dissolved the compound in 0.5% methyl cellulose and got a suspension, it is fine. And 0.2% Tween 80 can help the suspension dissolving more homogeneous.

Bcr-Abl Signaling Pathway Map

Bcr-Abl Inhibitors with Unique Features

Selective Bcr-Abl Inhibitor

Nilotinib (AMN-107) : Bcr-Abl-selective, IC50<30 nM.
Most Potent Bcr-Abl Inhibitor

GZD824 : Bcr-Abl(WT), IC50=0.34 nM; Bcr-Abl(T315I), IC50=0.68 nM.
FDA-approved Bcr-Abl Inhibitor

Dasatinib : Approved by FDA for CML and Ph+ ALL.
Newest Bcr-Abl Inhibitor

GZD824 : Orally bioavailable Bcr-Abl inhibitor for Bcr-Abl(WT) and Bcr-Abl(T315I) with IC50 of 0.34 nM and 0.68 nM, respectively.

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Bafetinib (INNO-406)