CI-1040

The dual specific threonine/tyrosine kinase, map kinase kinase (MEK), is a key component of the RAS/RAF/MEK/ERK signaling pathway that is frequently activated in human tumors.{6694,16830} CI-1040 is a benzhydroxamate compound that potently inhibits MEK in an in vitro mitogen-activated protein kinase cascade assay with an IC50 value of 2.3 nM (Kd = 74 nM when activated with adenosine triphosphate).{16877,15629} It can suppress phosphorylation of ERK in mouse colon 26 tumors with an IC50 value of 35 nM and demonstrates in vivo activity with oral administration in a mouse tumor model.{16877} The second-generation MEK inhibitor PD 0325901 (Item No. 13034) is a structural derivative of CI-1040 that was developed for improved solubility.{16877}