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| 25mg |
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| 50mg |
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| 100mg |
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Lyn-IN-1 (Bafetinib analogue), also known as INNO-406 analog and NS-187 analog, is a potent and selective dual Bcr-Abl/Lyn inhibitor, disclosed in patent WO2014169128A1.
| ln Vitro |
Bafetinib inhibits WT Bcr-Abl autophosphorylation and downstream kinase activity in K562 and 293T cells, with IC50 values of 11 nM and 22 nM, respectively. Without affecting the growth of the Bcr-Abl-negative U937 cell line, bafetinib potently inhibits the growth of Bcr-Abl-positive cell lines, such as K562, KU812, and BaF3/wt cells. Additionally, bafetinib shows antiproliferative activity against Bcr-Abl point mutant cell lines, like BaF3/E255K cells, in a dose-dependent manner.[1] Bafetinib inhibits Bcr-Abl phosphorylation, which results in caspase-mediated and caspase-independent cell death in Bcr-Abl+ leukemia cell lines.[2]
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|---|---|
| ln Vivo |
Bafetinib (0.2 mg/kg/day) significantly and completely inhibits tumor growth in the Bcr-Abl–positive KU812 mouse model, with no side effects at doses up to 20 mg/kg/day. Bafetinib has a maximal tolerated dose of 200 mg/kg/d and a bioavailability value (BA) of 32% in Balb/c mice.[1] Combining bafetinib (60 mg/kg) and cyclosporine A (CsA) (50 mg/kg) significantly inhibits leukemia growth in the brain when applied to a Central Nervous System (CNS) leukemia model containing Ba/F3/wt bcr-ablGFP, Ba/F3/Q252H, or Ba/F3/M351T cells.[3]
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| Enzyme Assay |
Bcr-Abl kinase assays are carried out using the SignaTECT protein tyrosine kinase assay system in 25 μL of reaction mixture that contains 250 μM peptide substrate, 740 Bq/μL [γ-33P]ATP, and 20 μM cold adenosine triphosphate (ATP). Ten nanometers of each Bcr-Abl kinase are used. Using an enzyme-linked immunosorbent assay (ELISA) kit, kinase tests are performed for Abl, Src, and Lyn. KinaseProfiler is used to assess NS-187's inhibitory effects on 79 tyrosine kinases.
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| Cell Assay |
In 96-well plates, K562, BaF3/wt, BaF3/E255K, and BaF3/T315I cells are plated at a density of 1 × 103, while KU812 and U937 cells are plated at a density of 5 × 103. Bafetinib is serially diluted and incubated with cells for three days. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Nacalai Tesque) assay is used to measure cell proliferation. The data is fitted to a logistic curve to determine the 50% inhibitory concentration (IC50) values.
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| Animal Protocol |
KU812 xenograft is established by subcutaneous injection of KU812 cells into the right flank of Balb/c-nu/nu female mice.
≤20 mg/kg/day Administered via p.o. |
| References | |
| Additional Infomation |
See also: Bafetinib (annotation moved to).
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| Molecular Formula |
C30H31F3N8O
|
|---|---|
| Molecular Weight |
576.6154
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| Exact Mass |
576.257
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| Elemental Analysis |
C, 62.49; H, 5.42; F, 9.88; N, 19.43; O, 2.77
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| CAS # |
887650-05-7
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| Related CAS # |
887650-05-7; 859212-16-1
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| PubChem CID |
24853523
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| Appearance |
white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.640
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| LogP |
3.03
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
42
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| Complexity |
864
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(N1CC[C@H](N(C)C)C1)C1C=CC(C(=O)NC2C=CC(C)=C(NC3N=CC(C4C=NC=NC=4)=CN=3)C=2)=CC=1C(F)(F)F
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| InChi Key |
ZOPBZHLJXQAQON-VWLOTQADSA-N
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| InChi Code |
InChI=1S/C30H31F3N8O/c1-19-4-7-24(11-27(19)39-29-36-14-23(15-37-29)22-12-34-18-35-13-22)38-28(42)20-5-6-21(26(10-20)30(31,32)33)16-41-9-8-25(17-41)40(2)3/h4-7,10-15,18,25H,8-9,16-17H2,1-3H3,(H,38,42)(H,36,37,39)/t25-/m0/s1
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| 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
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| Synonyms |
NS187; NS-187; NS 187; Bafetinib; INNO406; INNO 406; INNO-406
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ~50 mg/mL (86.7 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.34 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7342 mL | 8.6712 mL | 17.3424 mL | |
| 5 mM | 0.3468 mL | 1.7342 mL | 3.4685 mL | |
| 10 mM | 0.1734 mL | 0.8671 mL | 1.7342 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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