RDEA119 is an orally administered inhibitor of MEK, downstream from RAS in the MAPK pathway. It inhibits cell proliferation by arresting dividing cells in the G1 phase of the cell cycle.
NCI drug dictionary definition: RDEA119 is an orally bioavailable selective MEK inhibitor with potential antineoplastic activity. MEK inhibitor RDEA119 specifically inhibits mitogen-activated protein kinase kinase 1 (MAP2K1 or MAPK/ERK kinase 1), resulting in inhibition of growth factor-mediated cell signaling and tumor cell proliferation. MEK, a dual specificity threonine/tyrosine kinase, is a key component of the RAS/RAF/MEK/ERK signaling pathway that regulates cell growth; constitutive activation of this pathway has been implicated in many cancers.
Clinical Trials relevant to GIST:
RDEA119 and Sorafenib Combination Dose Escalation Study
This trial may be particularly relevant to patients with NF1 GIST, which has strong activation of the MAPK pathways. It might also be relevant to the few GIST patients with wildtype KIT and BRAF mutations.
An abstract of an ASCO 2008 Molecular Markers meeting presentation is available:
The effect of MEK inhibitor RDEA119 on biomarkers in advanced cancer patients in a phase I clinical trial
Several posters about RDEA119 presented at recent cancer meetings are available in pdf format: