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| 25mg |
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| Targets |
Lyn-IN-1 targets the Lyn kinase and Bcr-Abl kinase. Lyn is a member of the Src family of tyrosine kinases and plays a critical role in immune cell signaling, proliferation, and survival. By inhibiting Lyn, it disrupts downstream signaling pathways involved in inflammation and cancer. It is studied for its potential in treating thrombocytopenia.
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| 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]
In vitro, Lyn-IN-1 demonstrates potent inhibitory activity against its targets. As a dual Bcr-Abl/Lyn inhibitor, it shows strong activity in kinase assays. Its activity is confirmed in cell-based assays where it inhibits Lyn-mediated signaling. It shows promising anti-inflammatory and anti-cancer activities. Its IC50 values for the target kinases are characteristic of a potent inhibitor. |
| 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]
In vivo, Lyn-IN-1 is used as a preclinical research tool. It shows potential as a therapeutic agent for the treatment of various diseases, including cancer and immune-related disorders. Its ability to inhibit Lyn kinase makes it relevant for studying immune cell function and diseases where Lyn is dysregulated. Specific in vivo efficacy data are limited. |
| 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.
The in vitro kinase assay for Lyn-IN-1 involves measuring its ability to inhibit the phosphorylation activity of Lyn and Bcr-Abl kinases. The enzyme is incubated with a peptide substrate and ATP in the presence of varying concentrations of the compound. The amount of phosphorylated substrate is measured using a luminescent or fluorescent detection system, and the IC50 is calculated from the dose-response curve. |
| 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.
In vitro cell culture studies for Lyn-IN-1 utilize cancer cell lines or immune cells. Cells are treated with the compound, and cell viability is assessed using MTT assays. The phosphorylation of Lyn and its downstream substrates is measured by Western blotting to confirm target inhibition. Apoptosis and cell cycle analysis are performed by flow cytometry. |
| 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. In vivo animal experiments for Lyn-IN-1 are not extensively documented. However, its anti-inflammatory and anti-cancer activities could be evaluated in relevant disease models. For example, its efficacy in cancer could be tested in xenograft models. Its effects on immune function could be studied in models of autoimmune diseases or inflammation. |
| ADME/Pharmacokinetics |
Lyn-IN-1 has a molecular formula of C30H31F3N8O and a molecular weight of 576.62 g/mol. It is a solid compound that is soluble in DMSO. It is typically stored as a powder at -20°C for long-term stability. Its stability is maintained under recommended storage conditions. For in vivo studies, it may be formulated in a suitable vehicle.
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| Toxicity/Toxicokinetics |
Toxicological data for Lyn-IN-1 are limited, as it is a research compound. It is not intended for human use. Comprehensive toxicity studies have not been reported. Standard safety precautions for handling chemical reagents should be followed. Its effects on Lyn kinase suggest it could have significant biological effects at higher doses.
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| References | |
| Additional Infomation |
See also: Bafetinib (note moved to).
Lyn-IN-1 is a research compound with no clinical approval. It is a valuable tool for studying Lyn kinase biology and its role in immune cell signaling, inflammation, and cancer. It is used in drug discovery programs to explore the therapeutic potential of Lyn inhibition for the treatment of cancer and immune-related disorders. |
| Molecular Formula |
C30H31F3N8O
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|---|---|
| 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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