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5mg |
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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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Other Sizes |
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Purity: ≥98%
PD184352 (PD-184352; CI-1040), an analog of benzhydroxamate, is an orally bioactive, specific, allosteric/non-ATP competitive MEK1/2 inhibitor with potential anticancer activity. In cell-based assays, it inhibits MEK1/2 with IC50 values of 17 nM and exhibits a 100-fold preference for MEK1/2 over MEK5. In mouse xenograft models, it exhibits strong in vitro anti-proliferative activity and significant in vivo antitumor efficacy.
Targets |
MEK1 (IC50 = 17 nM); MEK2 (IC50 = 17 nM)
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ln Vitro |
CI-1040 has an IC50 of 17 nM and directly inhibits MEK1. Additionally, a panel of related kinases with IC50 values more than 2.5 orders of magnitude higher has been shown to have little activity against it. The phosphorylation of ERK induced by mitogens is completely blocked when whole cells are treated with CI-1040. In MDA-MB-231 breast cancer cells, CI-1040 at a concentration of 1 μM is found to inhibit ERK1 and ERK2 phosphorylation by 99% and 92%, respectively[1]. In U-937 cells, CI-1040 causes apoptosis and blocks proliferation in a dose- and time-dependent manner. PUMA mRNA and protein levels significantly rise in response to CI-1040[2].
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ln Vivo |
The systemic administration of the MEK inhibitor CI-1040 significantly improves lung structure while cutting adenoma formation by one-third. Without obviously having an impact on pneumocyte differentiation, CL-1040-treated mice have less lung cell proliferation[3].
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Enzyme Assay |
Myelin basic protein (MBP) is phosphorylated by activated MAP kinase after it has been activated by MEK.When glutathione S-transferase (GST) fusion proteins made of the 44-kDa MAPK (GST-MAPK) or the 45-kDa MEK (GST-MEK1) are present, the incorporation of 32P into myelin basic protein (MBP) is measured. Assays are carried out in 50 mL of 50 mM Tris, pH 7.4, 10 mM MgCl2, 2 mM EGTA, and 10 μM [γ-32P]ATP containing 10 μg of GST-MEK1, 0.5 μg of GST-MAPK, and 40 μg of MBP. Reactions are stopped by adding Laemmli SDS sample buffer after 15 minutes of incubation at 30°C. SDS/10% PAGE resolves phosphorylated MBP. The result of this screening process is the identification of several small-molecule MEK inhibitors, including CI-1040. With a 50% inhibitory concentration (IC50) of 17 nM, experiments examining the order of addition reveal that CI-1040 directly inhibits MEK1 without affecting the activity of MAPK.
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Cell Assay |
In cell culture, the MEK inhibitor CI-1040 is used at a final concentration of 50 mg/mL after being dissolved in DMSO as 10 mM stock solutions. After pretreatment with 5 and 20 uM CI-1040 for 24 hours, U-937 cells are transfected for 48 hours with either wt-p53 siRNA or PUMA siRNA. Then each well receives 20 mL of the MTT solution, and the process is repeated for a further 2 hours. In order to dissolve the MTT formazan produced by metabolically viable cells in 100 mL of isopropanol, the supernatant is aspirated after the experiment is finished. A plate reader is used to measure absorbance at 595 nm after the plates have been mixed for 30 minutes on a gyratory shaker[2].
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Animal Protocol |
Mice: By administering constitutively active C-Raf kinase to the lung, a lung cancer mouse model is produced. A daily intraperitoneal injection of BAY 43-9006 or CI-1040 is given starting at the age of 4 months for a total of 21 days at a dose of 100 mg/kg. At the conclusion of the treatment period, the lungs were separated and examined[3].
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References |
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Molecular Formula |
C17H14CLF2IN2O2
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Molecular Weight |
478.67
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Exact Mass |
477.98
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Elemental Analysis |
C, 42.66; H, 2.95; Cl, 7.41; F, 7.94; I, 26.51; N, 5.85; O, 6.69
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CAS # |
212631-79-3
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Related CAS # |
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Appearance |
Solid powder
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SMILES |
C1CC1CONC(=O)C2=C(C(=C(C=C2)F)F)NC3=C(C=C(C=C3)I)Cl
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InChi Key |
GFMMXOIFOQCCGU-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C17H14ClF2IN2O2/c18-12-7-10(21)3-6-14(12)22-16-11(4-5-13(19)15(16)20)17(24)23-25-8-9-1-2-9/h3-7,9,22H,1-2,8H2,(H,23,24)
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Chemical Name |
2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide
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Synonyms |
PD 184352; CI-1040; CI1040; PD-184352; PD184352; CI 1040
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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 |
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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 (5.22 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: ≥ 2.08 mg/mL (4.35 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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 30% PEG400+0.5% Tween80+5% propylene glycol, pH 9: 10mg/mL |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0891 mL | 10.4456 mL | 20.8912 mL | |
5 mM | 0.4178 mL | 2.0891 mL | 4.1782 mL | |
10 mM | 0.2089 mL | 1.0446 mL | 2.0891 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.