Antibodies
Bafetinib (INNO-406)
- 貨號 Cat. No.
- S1369
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
Bafetinib (INNO-406)
Catalog No.S1369
Bafetinib (INNO-406) is a potent and selective dual Bcr-Abl/Lyn inhibitor with IC50 of 5.8 nM/19 nM, does not inhibit the phosphorylation of the T315I mutant and is less potent to PDGFR and c-Kit. Phase 2.
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Biological Activity
| Description | Bafetinib (INNO-406) is a potent and selective dual Bcr-Abl/Lyn inhibitor with IC50 of 5.8 nM/19 nM, does not inhibit the phosphorylation of the T315I mutant and is less potent to PDGFR and c-Kit. Phase 2. | |||||
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| Targets | Abl | Lyn | ||||
| IC50 | 5.8 nM | 19 nM [1] | ||||
| 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] | |||||
| Features | Dual Bcr-Abl/Lyn inhibitor. | |||||
Protocol(Only for Reference)
Kinase Assay: [1]
| 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. |
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Cell Assay: [1]
| Cell lines | K562, BaF3/wt, BaF3/E255K, and BaF3/T315I cells |
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| 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. |
Animal Study: [1]
| Animal Models | KU812 xenograft is established by subcutaneous injection of KU812 cells into the right flank of Balb/c-nu/nu female mice. |
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| Dosages | ≤20 mg/kg/day |
| Administration | Administered via p.o. |
| Solubility | 0.5% methylcellulose/0.2% Tween 80 30 mg/mL |
References
Clinical Trial Information( data from http://clinicaltrials.gov)
| NCT Number | Recruitment | Conditions | Sponsor /Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT00352677 | Completed | Chronic Myeloid Leukemia|Acute Lymphocytic Leukemia | CytRx | 2006-07 | Phase 1 |
| NCT01144260 | Completed | B-Cell Chronic Lymphocytic Leukemia | CytRx | 2010-06 | Phase 2 |
| NCT01215799 | Completed | Hormone Refractory Prostate Cancer | CytRx | 2010-08 | Phase 2 |
| NCT01234740 | Completed | Adult Anaplastic Astrocytoma|Adult Anaplastic Ependymoma|Adult Anaplastic Oligodendroglioma|Adult Giant Cell Glioblastoma|Adult Glioblastoma|Adult Gliosarcoma|Adult Mixed Glioma|Recurrent Adult Brain Tumor etc. | City of Hope Medical Center|National Cancer Institute (NCI) | 2010-12 |
Chemical Information
Download Bafetinib (INNO-406) SDF
| Molecular Weight (MW) | 576.62 |
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| Formula | C30H31F3N8O |
| CAS No. | 859212-16-1 |
| Storage | 3 years -20℃Powder |
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| 6 months-80℃in DMSO | |
| Syonnyms | NS-187 |
| Solubility (25°C) * | In vitro | DMSO | 115 mg/mL (199 mM) |
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| Water | <1 mg/mL (<1 mM) | ||
| Ethanol | <1 mg/mL (<1 mM) | ||
| In vivo | 0.5% methylcellulose/0.2% Tween 80 | 30 mg/mL | |
| * <1 mg/ml means slightly soluble or insoluble. * 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 Name | (S)-4-((3-(dimethylamino)pyrrolidin-1-yl)methyl)-N-(4-methyl-3-(4-(pyrimidin-5-yl)pyrimidin-2-ylamino)phenyl)-3-(trifluoromethyl)benzamide |
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Preparing Stock Solutions
| Stock Solution (1ml DMSO) | 1mM | 10mM | 20mM | 30mM |
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| Mass(mg) | 0.57662 | 5.7662 | 11.5324 | 17.2986 |
