PD184352 (CI-1040)

Names

[ Name ]:
PD184352 (CI-1040)

[Synonym ]:
Benzamide, 2-[(2-chloro-4-iodophenyl)amino]-N-(cyclopropylmethoxy)-3,4-difluoro-
CI-1040
2-[(2-Chloro-4-iodophenyl)amino]-N-(cyclopropylmethoxy)-3,4-difluorobenzamide
2-(2-Chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide CI-1040
2-((2-Chloro-4-iodophenyl)amino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide
2-(2-chloro-4-iodophenylamino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide

Biological Activity

[Description]:

CI-1040 (PD184352) is an orally active, highly specific, small-molecule inhibitor of MEK with an IC50 of 17 nM for MEK1.

[Related Catalog]:

Signaling Pathways >> MAPK/ERK Pathway >> MEK

Research Areas >> Cancer

[Target]

MEK1:17 nM (IC50)

[In Vitro]

CI-1040 directly inhibits MEK1 with an IC50 of 17 nM. It has also been shown to have little activity against a panel of related kinases with IC50 values more than 2.5 orders of magnitude higher. Treatment of whole cells with CI-1040 completely inhibits the mitogen-stimulated phosphorylation of ERK. CI-1040 at a concentration of 1 μM is found to inhibit phosphorylation of ERK1 and ERK2 by 99% and 92%, respectively in MDA-MB-231 breast cancer cells[1]. CI-1040 induces apoptosis and inhibits proliferation in U-937 cells in a dose and time-dependent manner. CI-1040 induces a significant increase in PUMA mRNA and protein levels[2].

[In Vivo]

The systemic administration of the MEK inhibitor CI-1040 reduces adenoma formation to a third and significantly restores lung structure. The proliferation rate of lung cells of mice treated with CL-1040 is decreased without any obvious effects on differentiation of pneumocytes[3].

[Cell Assay]

The MEK inhibitor CI-1040 is dissolved in DMSO as 10 mM stock solutions and used in cell culture at final concentration 50 mg/mL. U-937 cells are pretreated for 24 hrs with 5 and 20 uM CI- 1040, then transfected with wt-p53 siRNA or PUMA siRNA for 48 hrs. Then 20 mL of MTT solution are added to each well and incubated further for 2 hours. Upon termination, the supernatant is aspirated and the MTT formazan formed by metabolically viable cells is dissolved in 100 mL of isopropanol. The plates are mixed for 30 minutes on a gyratory shaker, and absorbance is measured at 595 nm using a plate reader[2].

[Animal admin]

Mice: The lung cancer mouse model is generated by targeting constitutively active C-Raf kinase to the lung. BAY 43-9006 or CI-1040 is daily intraperitoneal injected at a dose of 100 mg/kg from 4 months of age over a period of 21 days. Lungs were isolated and analyzed at the end of the treatment period[3].

[References]

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

[2]. Wei CR, et al. 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]. Kramer BW, et al. 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.

[Related Small Molecules]

U0126-EtOH | PD98059 | Trametinib (GSK1120212) | PD0325901 | Selumetinib (AZD6244) | Cobimetinib | MEK162(ARRY-162,ARRY-438162) | RO 5126766 | Isorhamnetin | AS703026 | RGB-286638 | BIX02188 | BIX02189 | SL-327 | TAK-733

Chemical & Physical Properties

[ Density]:
1.7±0.1 g/cm3

[ Melting Point ]:
166-169ºC

[ Molecular Formula ]:
C₁₇H₁₄ClF₂IN₂O₂

[ Molecular Weight ]:
478.659

[ Exact Mass ]:
477.975647

[ PSA ]:
50.36000

[ LogP ]:
8.01

[ Index of Refraction ]:
1.656

[ Storage condition ]:
-20°C Freezer

[ Water Solubility ]:
DMSO: ≥30mg/mL

Safety Information

[ Symbol ]:

GHS09

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H400

[ Precautionary Statements ]:
P273

[ Hazard Codes ]:
N

[ Risk Phrases ]:
50/53

[ Safety Phrases ]:
60-61

[ RIDADR ]:
UN 3077 9 / PGIII

[ HS Code ]:
2924299090

Customs

[ HS Code ]: 2924299090

[ Summary ]:
2924299090. other cyclic amides (including cyclic carbamates) and their derivatives; salts thereof. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

Articles

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Cancer Prev. Res. (Phila.) 7(12) , 1240-50, (2014)

This study proposes to investigate quercetin antitumor efficacy in vitro and in vivo, using the P39 cell line as a model. The experimental design comprised leukemic cells or xenografts of P39 cells, t...

BAFF activation of the ERK5 MAP kinase pathway regulates B cell survival.

J. Exp. Med. 212 , 883-92, (2015)

B cell activating factor (BAFF) stimulation of the BAFF receptor (BAFF-R) is essential for the homeostatic survival of mature B cells. Earlier in vitro experiments with inhibitors that block MEK 1 and...

Mechanisms of tolvaptan-induced toxicity in HepG2 cells.

Biochem. Pharmacol. 95 , 324-36, (2015)

Tolvaptan, a vasopressin receptor 2 antagonist used to treat hyponatremia, has recently been reported to be associated with an increased risk of liver injury. In this study, we explored the underlying...

Related Compounds

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