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In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
PD184352 (also known as CI-1040), a benzhydroxamate derivative, is a potent and highly selective MEK1/2, two members of the family of MAPKKs, inhibitor that inhibits purified MEK1 with IC50 of 17 nM in a non-ATP and non-ERK1/2 competitive manner [1].
PD184352 binds to a hydrophobic pocket, which is located in a region with low sequence homology to other kinases, adjacent to the Mg-ATP binding site of MEK1 and MEK2 inducing a conformational change in un-phosphorylated MEK1/2 and hence inactivating the un-phosphorylated MEK1/2 [1].
PD184352 has been found to be actively against tumors, where it inhibits the growth of colon carcinomas in mouse xenograft models [1].
References:[1] Frémin C, Meloche S. From basic research to clinical development of MEK1/2 inhibitors for cancer therapy. J Hematol Oncol. 2010 Feb 11;3:8. doi: 10.1186/1756-8722-3-8.
Cell lines
CCl39 cells expressing FLAG-ERK5
Preparation method
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions
IC50: < 1 μM, 90 min
Applications
Cells were serum-starved for 16 h prior to the addition of PD184352, or an equivalent of DMSO vehicle control for 90 min. Single dishes of cells were then stimulated with 10% FBS for 15 min and immune-complex kinase assays performed with either myelin basic protein (MBP; ERK1) or GST-MEF2C (ERK5), as a substrate. PD184352 inhibited FBS-induced ERK1 activation with an IC50 below 1 μM, whereas even a dose of 20 μM PD184352 was insufficient to inhibit ERK5 activity, induced in the same manner and assayed from the same cell extracts as ERK1.
Animal models
DBA/2-pcy/pcy mice
Dosage form
Oral administration, 400 mg/kg daily for the first week and then every third day for 6 additional weeks
The body weight of the PD184352-treated pcy mice was slightly but significantly lower than that of the control pcy mice. The kidney weight, kidney weight to body weight ratio, BP, and serum creatinine levels of the PD184352-treated pcy mice also were significantly less at the end of treatment. Water intake of PD184352-treated pcy mice was reduced, and urine osmolality was increased. The cystic index also was significantly lower in the PD184352-treated pcy mice than in the control pcy mice.
Other notes
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References:
[1] SQUIRES M, NIXON P, COOK S. Cell-cycle arrest by PD184352 requires inhibition of extracellular signal-regulated kinases (ERK) 1/2 but not ERK5/BMK1. Biochem. J, 2002, 366: 673-680.
[2] Omori S, Hida M, Fujita H, et al. Extracellular signal–regulated kinase inhibition slows disease progression in mice with polycystic kidney disease. Journal of the American Society of Nephrology, 2006, 17(6): 1604-1614.
