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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK).

Several key growth factors, cytokines, and proto-oncogenes transduce their growth- and differentiation-promoting signals through the mitogen-activated protein kinase or extracellular signal-regulated protein kinase ( ERK) cascade. Overexpression or constitutive activation of this pathway has been shown to play an important role in the pathogenesis and progression of breast and other cancers, making the components of this signaling cascade potentially important as therapeutic targets. CI-1040 (PD184352) is an orally active, highly specific, small-molecule inhibitor of one of the key components of this pathway (MEK1/MEK2), and thereby effectively blocks the phosphorylation of ERK and continued signal transduction through this pathway. Antitumor activity has been seen in preclinical models with this compound, particularly for pancreas, colon, and breast cancers, which has been shown to correlate with its inhibition of pERK. Clinically, CI-1040 has been shown to be well tolerated in phase I studies, with safety and pharmacokinetic profiles that permit continuous daily dosing. Biomarker studies have shown target inhibition in patients, and antitumor activity has also been observed with a partial response in one patient with pancreatic cancer and stable disease in approximately 25% of phase I patients. Given the central role of the ERK/mitogen-activated protein kinase pathway in mediating growth-promoting signals for a diverse group of upstream stimuli, inhibitors of MEK, as a key central mediator, could have significant clinical benefit in the treatment of breast and other cancers.[1]


  1. CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Allen, L.F., Sebolt-Leopold, J., Meyer, M.B. Semin. Oncol. (2003) [Pubmed]
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