CI-1040 (PD184352)

Cas No.:	212631-79-3
Chemical Name:	2-(2-Chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide
Synonyms:	2-((2-Chloro-4-iodophenyl)amino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide;2-(2-Chloro-4-iodophenylamino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide;PD184352 (CI-1040);Benzamide, 2-[(2-chloro-4-iodophenyl)amino]-N-(cyclopropylmethoxy)-3,4-difluoro-;CI-1040;CI-1040 (PD184352);PD 184,352;PD 184352 (PD184352 ,CI-1040);PD-184352;2-(2-Chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide CI-1040;CI1040;2-(2-Chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide;2-(2-Chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide;PD184352;PD 184352;CI 1040;R3K9Y00J04;C.I. 1040;DSSTox_RID_83140;DSSTox_CID_28871;DSSTox_GSID_48945;C17H14ClF2IN2O2;2-(
SMILES:	IC1C([H])=C([H])C(=C(C=1[H])Cl)N([H])C1C(=C(C([H])=C([H])C=1C(N([H])OC([H])([H])C1([H])C([H])([H])C1([H])[H])=O)F)F
Formula:	C17H14ClF2In2O2
M.Wt:	478.6595
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

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