CI-1040

CI-1040 (PD 184352) is an orally active, highly specific, small-molecule inhibitor of MEK with an IC₅₀ of 17 nM for MEK1. IC50 & Target:IC50: 17 nM (MEK)^[1] 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].