PD184352 (CI1040)

Alias: PD 184352; CI-1040; CI1040; PD-184352; PD184352; CI 1040
Cat No.:V0448 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.
PD184352 (CI1040) Chemical Structure CAS No.: 212631-79-3
Product category: MEK
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

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.

Biological Activity I Assay Protocols (From Reference)
Targets
MEK1 (IC50 = 17 nM); MEK2 (IC50 = 17 nM)
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].
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].
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.
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].
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].
References

[1]. CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Semin Oncol. 2003 Oct;30(5 Suppl 16):105-16.

[2]. MEK inhibitor CI-1040 induces apoptosis in acute myeloid leukemia cells in vitro. Eur Rev Med Pharmacol Sci. 2016 May;20(10):1961-8.

[3]. Use of mitogenic cascade blockers for treatment of C-Raf induced lung adenoma in vivo: CI-1040strongly reduces growth and improves lung structure. BMC Cancer. 2004 Jun 1;4:24.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C17H14CLF2IN2O2
Molecular Weight
478.67
Exact Mass
477.98
Elemental Analysis
C, 42.66; H, 2.95; Cl, 7.41; F, 7.94; I, 26.51; N, 5.85; O, 6.69
CAS #
212631-79-3
Appearance
Solid powder
SMILES
C1CC1CONC(=O)C2=C(C(=C(C=C2)F)F)NC3=C(C=C(C=C3)I)Cl
InChi Key
GFMMXOIFOQCCGU-UHFFFAOYSA-N
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)
Chemical Name
2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide
Synonyms
PD 184352; CI-1040; CI1040; PD-184352; PD184352; CI 1040
HS Tariff Code
2934.99.9001
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)
Solubility Data
Solubility (In Vitro)
DMSO: ~96 mg/mL (~200.6 mM)
Water: <1 mg/mL
Ethanol: ~14 mg/mL (~29.2 mM)
Solubility (In Vivo)
30% PEG400+0.5% Tween80+5% propylene glycol, pH 9: 10mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
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.

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