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| 2mg |
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| 25mg |
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Purity: ≥98%
Gandotinib (formerly also known as LY2784544) is a novel, potent and selective JAK2 (Janus kinase) inhibitor with potential antitumor activity. It inhibits JAK2 with an IC50 of 3 nM, and shows 8- and 20-fold selectivity for JAK2 over JAK1 and JAK3. It shows potent in vitro antiproliferative activity and high in vivo antitumor efficacy. Gandotinib effectively inhibited JAK2V617F-driven signaling and cell proliferation in Ba/F3 cells (IC50=20 and 55 nM, respectively). In vivo, Gandotinib effectively inhibited STAT5 phosphorylation in Ba/F3-JAK2V617F-GFP ascitic tumor cells and significantly reduced Ba/F3-JAK2V617F-GFP tumor burden in the JAK2V617F-induced MPN model.
| ln Vitro |
Gandotinib (LY2784544) is a strong, ATP-competitive, and selective inhibitor of the tyrosine kinase known as Janus kinase 2 (JAK2). In Ba/F3 cells, LY2784544 potently suppresses JAK2V617F-driven signaling and cell proliferation (IC50=20 and 55 nM, respectively). By contrast, Gandotinib (LY2784544) has a substantially lower potency (IC50=1183 and 1309 nM, respectively) at suppressing interleukin-3-stimulated wild-type JAK2-mediated signaling and cell proliferation. Interestingly, geldotinib (LY2784544) exhibits relatively little efficacy against IL-3-activated wild-type JAK2 signaling, with an IC50 of 1183 nM, but potently inhibiting JAK2V617F signaling (IC50 = 20 nM). Gandotinib (LY2784544) is a strong inhibitor of the proliferation of IL-3-stimulated wild-type JAK2 expressing Ba/F3 cells (IC50=1309 nM). LY2784544 inhibits the proliferation of JAK2V617F-expressing cells (IC50=55 nM) and is significantly less. In the NK-92 JAK3/JAK1 heterodimer assay (942 nM), ganditinib (LY2784544) exhibited the required threshold selectivity and is potent in the cell-based TF-1 JAK2 assay (IC50=45 nM)[1].
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| ln Vivo |
Gandotinib (LY2784544) considerably (P<0.05) lowers the tumor burden of Ba/F3-JAK2V617F-GFP in the JAK2V617F-induced MPN model (TED50=13.7 mg/kg, twice daily) and efficiently inhibits STAT5 phosphorylation in Ba/F3-JAK2V617F-GFP (green fluorescent protein) ascitic tumor cells (TED50=12.7 mg/kg)[1].
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| Animal Protocol |
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| References |
[1]. Ma L, et al. Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F. Blood Cancer J. 2013, 3, e109
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| Molecular Formula |
C23H25CLFN7O
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| Molecular Weight |
469.94
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| CAS # |
1229236-86-5
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| Related CAS # |
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| SMILES |
ClC1C([H])=C([H])C(=C(C=1[H])F)C([H])([H])C1=C(C([H])([H])[H])N=C2C(=C([H])C(N([H])C3C([H])=C(C([H])([H])[H])N([H])N=3)=NN21)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H]
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| InChi Key |
SQSZANZGUXWJEA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H25ClFN7O/c1-14-9-21(29-28-14)27-22-11-17(13-31-5-7-33-8-6-31)23-26-15(2)20(32(23)30-22)10-16-3-4-18(24)12-19(16)25/h3-4,9,11-12H,5-8,10,13H2,1-2H3,(H2,27,28,29,30)
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| Chemical Name |
3-(4-chloro-2-fluorobenzyl)-2-methyl-N-(3-methyl-1H-pyrazol-5-yl)-8-(morpholinomethyl)imidazo[1,2-b]pyridazin-6-amine
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.32 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 (5.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1279 mL | 10.6397 mL | 21.2793 mL | |
| 5 mM | 0.4256 mL | 2.1279 mL | 4.2559 mL | |
| 10 mM | 0.2128 mL | 1.0640 mL | 2.1279 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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