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

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