Aidan G. Gilmartin

TL;DR: GSK1120212 combines high potency, selectivity, and long circulating half-life, offering promise for successfully targeting the narrow therapeutic window anticipated for clinical MEK inhibitors.

TL;DR: Human Chk1 is a recently identified homologue of the Schizosaccharomyces pombe checkpoint kinase gene, which is required for G2 arrest in response to DNA damage, and a potent and selective indolocarbazole inhibitor of Chk 1 kinase activity is identified and used to assess cell cycle checkpoint responses.

TL;DR: Inhibition of CENP-E motor activity in cultured cells and tumor xenografts caused failure of metaphase chromosome alignment and induced mitotic arrest, indicating that tight binding of C Enp-E to microtubules is insufficient to satisfy the mitotic checkpoint.

TL;DR: GSK2830371 is the first orally active, allosteric inhibitor of Wip1 phosphatase, an oncogenic phosphat enzyme common to multiple cancers and results in expected pharmacodynamic effects and causes inhibition of lymphoma xenograft growth.

TL;DR: It is confirmed that the antiproliferative activity correlates with cellular MEK inhibition and observed significant antitumor activity with daily oral dosing of 1 in a tumor xenograft model, which led to the selection of 1 for clinical development.