Linifanib (ABT-869) (Synonyms: Linifanib) |
| カタログ番号GC17958 |
リニファニブ (ABT-869) (ABT-869) は、KDR、FLT1、PDGFRβ、および FLT3 に対してそれぞれ 4、3、66、および 4 nM の IC50 を有する VEGFR および PDGFR ファミリーの強力で経口的に活性な多標的阻害剤です。 .リニファニブ (ABT-869) は、顕著な抗腫瘍活性を示します。リニファニブ (ABT-869) は、無関係な RTK、可溶性チロシンキナーゼ、またはセリン/スレオニンキナーゼに対する活性がはるかに低くなります。リニファニブ (ABT-869) は、miR-10b の生合成をブロックする特異的な miR-10b 阻害剤です。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 796967-16-3
Sample solution is provided at 25 µL, 10mM.
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Linifanib (ABT-869) is an effective ATP-competitive tyrosine kinase inhibitor against the platelet-derived growth factor (PDGF) receptor and the vascular endothelial growth factor receptor (VEGFR) families, including constitutively active FMS-like receptor tyrosine kinase 3 (FLT3) [1][2]. It is of IC50 values of 0.55 nmol/L and 6 μmol/L to the cell growth in Ba/F3 FLT3 ITD mutant cells and in Ba/F3 FLT3 WT cells, respectively [1].
FLT3 is important in controlling the proliferation and differentiation of hematopoietic cells. Patients with acute myeloid leukemia (AML) showed activating mutations in FLT3. These mutations caused abnormal cell proliferation [1].
Linifanib at a concentration of 10 nmol/L induced apoptosis in internal tandem duplication (ITD) mutant cells, but showed no effect in WT cells. Treatment with linifanib did not differentiate WT cells from FLT3 mutant cells with mutation at D835V, in inhibiting proliferation or reducing cell viability. In Ba/F3 FLT3 ITD cell lines, linifanib at a concentration of 10 nmol/L, effectively inhibited the phosphorylation of FLT3. 10 nmol/L linifanib reduced the phosphorylation of Akt at Ser473 [1].
Daily orally treatment with linifanib by gavage in NOD/SCID mice with ITD mutant cell decreased the leukemia progression rate compared with the control. On day 7, ITD mutant cells showed rapid progression in control mice, whereas linifanib-treated mice showed no detectable disease. In addition, daily linifanib-treated mice with ITD mutant cells showed significantly longer (P < 0.01) survival duration than control mice with ITD mutant cells only [1].
References:
[1]. Jenny E. Hernandez-Davies, Joan P. Zape, Elliot M. Landaw, et al. The Multitargeted Receptor Tyrosine Kinase Inhibitor Linifanib (ABT-869) Induces Apoptosis through an Akt and Glycogen Synthase Kinase 3β–Dependent Pathway. Mol. Cancer Ther., 2011, 10(6):949-59.
[2]. Joyce E. Ohm, Michael R. Shurin, Clemens Esche, et al. Effect of Vascular Endothelial Growth Factor and FLT3 Ligand on Dendritic Cell Generation In Vivo. Journal of Immunology, 1999, 163:3260-3268.
| Cell experiment [1]: | |
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Cell lines |
Ba/F3 FLT3 ITD mutant and WT cells |
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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 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months. |
|
Reacting condition |
0.1 nM ~ 10 μM; 24 hrs |
|
Applications |
Linifanib was more effective at inhibiting cell growth in ITD mutant cells with the IC50 value of 0.55 nM. In addition, treatment with 10 nM of Linifanib induced apoptosis in ITD mutant cells, but showed no observable effect on WT cells. |
| Animal experiment [1]: | |
|
Animal models |
NOD/SCID mice with ITD mutant cells |
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Dosage form |
0.2 mL/20 g; p.o.; q.d. |
|
Applications |
In NOD/SCID mice with ITD mutant cells, Linifanib decreased leukemia progression. On day 7, untreated mice exhibited rapid progression of ITD mutant cells, whilst mice treated with Linifanib showed no detectable disease. In addition, Linifanib significantly prolonged survival duration of Ba/F3 FLT3 ITD-injected mice. |
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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]. Jenny E. Hernandez-Davies, Joan P. Zape, Elliot M. Landaw, et al. The Multitargeted Receptor Tyrosine Kinase Inhibitor Linifanib (ABT-869) Induces Apoptosis through an Akt and Glycogen Synthase Kinase 3β–Dependent Pathway. Mol. Cancer Ther., 2011, 10(6):949-59. | |
| Cas No. | 796967-16-3 | SDF | |
| 同義語 | Linifanib | ||
| Chemical Name | 1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea | ||
| Canonical SMILES | CC1=CC(=C(C=C1)F)NC(=O)NC2=CC=C(C=C2)C3=C4C(=CC=C3)NN=C4N | ||
| Formula | C21H18FN5O | M.Wt | 375.41 |
| 溶解度 | ≥ 18.75mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6638 mL | 13.3188 mL | 26.6375 mL |
| 5 mM | 0.5328 mL | 2.6638 mL | 5.3275 mL |
| 10 mM | 0.2664 mL | 1.3319 mL | 2.6638 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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Calculation results:
Working concentration: mg/ml;
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.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, 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.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 5 reference(s) in Google Scholar.)
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