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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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1g |
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L-779450 is a potent, selective and ATP-competitive Raf kinase inhibitor (IC50 = 10 nM). L-779450 causes apoptosis and suppresses DNA synthesis in cells that multiply in response to Raf-1 and A-Raf but not B-Raf.
Targets |
B-Raf (Kd = 2.4 nM); B-Raf (IC50 = 10 nM)
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ln Vitro |
L-779450 (L-779,450) shows a high degree of specificity towards Raf. Only one other tested kinase, p38MAPK, which shares a kinase domain with Raf structurally, was inhibited. At doses ranging from 0.3 to 2 μM, L-779450 inhibits the anchorage-independent growth of human tumor lines[2]. The effects of L-779450 (L-779,450) on TRAIL sensitivity are investigated here in melanoma cell lines with high TRAIL sensitivity (A-375 and SK-Mel-147), moderate sensitivity (Mel-HO, SK-Mel-13, and SK-Mel-28), and permanent resistance (MeWo, Mel-2a, and SK-Mel-103), as well as in TRAIL-selected cell lines with acquired resistance (A-375-TS and Mel-HO-TS). L-779450 has only mild direct effects on apoptosis, but it significantly increases TRAIL-induced apoptosis in melanoma cells that are susceptible to it and overcomes TRAIL resistance in Mel-2a, SK-Mel-103, A-375-TS, and Mel-HO-TS. 16–35% of cells induce apoptosis at 24 hours[3].
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Cell Assay |
TRAIL (20 ng/mL), the pan-RAF inhibitor L-779450 (0.1–50 μM), the MEK inhibitor U0126 (20 M), and the selective BRAF(V600E) inhibitor Vemurafenib/PLX4032 are all used to induce apoptosis. The xCELLigence system is used for ongoing cell growth monitoring. Cell numbers that are attached correspond to relative cell indices. Analyses of the cell cycle are carried out to quantify apoptosis and cell cycle arrest. Propidium iodide (200 mg/mL) is used to stain trypsinized cells for 1 hour, and flow cytometry is used to quantify sub-G1 fractions, which represent cells with DNA fragments.
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References |
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Molecular Formula |
C20H14CLN3O
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Molecular Weight |
347.8
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Exact Mass |
347.08254
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Elemental Analysis |
C, 69.07; H, 4.06; Cl, 10.19; N, 12.08; O, 4.60
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CAS # |
303727-31-3
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Related CAS # |
303727-31-3
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Appearance |
Solid powder
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SMILES |
C1=CC=C(C=C1)C2=NC(=C(N2)C3=CC=NC=C3)C4=CC(=C(C=C4)Cl)O
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InChi Key |
WXJLXRNWMLWVFB-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C20H14ClN3O/c21-16-7-6-15(12-17(16)25)19-18(13-8-10-22-11-9-13)23-20(24-19)14-4-2-1-3-5-14/h1-12,25H,(H,23,24)
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Chemical Name |
2-chloro-5-(2-phenyl-5-pyridin-4-yl-1H-imidazol-4-yl)phenol
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Synonyms |
L779450; L 779450; L-779450; L 779,450; L-779,450; L779,450
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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: 70~100 mg/mL (201.3~287.5 mM)
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.19 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 (7.19 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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 (7.19 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 | 2.8752 mL | 14.3761 mL | 28.7522 mL | |
5 mM | 0.5750 mL | 2.8752 mL | 5.7504 mL | |
10 mM | 0.2875 mL | 1.4376 mL | 2.8752 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.