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Cytokinetics Announces the Initiation of a Phase I Clinical Trial for GSK-923295

16 Aug 2007 - Cytokinetics, Incorporated announced that GlaxoSmithKline (GSK) has initiated a first-time-in-humans Phase I clinical trial of GSK-923295 in patients with solid tumors. GSK-923295 is a small-molecule inhibitor of centromere-associated protein E (CENP-E). As reported at the 2007 Annual Meeting of the American Association for Cancer Research (AACR), GSK-923295 demonstrated a broad spectrum of activity against a range of human tumor xenografts grown in nude mice, including models of colon, breast, ovarian, lung and other tumors. The initiation of this clinical trial triggers a milestone payment of $1 million from GSK to Cytokinetics under the terms of the companies' strategic alliance established in June 2001.
 
This Phase I clinical trial is an open-label, non-randomized, dose-finding trial designed to investigate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of GSK-923295 in patients with advanced solid tumors. GSK-923295 is the third novel drug candidate to arise from Cytokinetics' broad strategic alliance with GSK.
 
CENP-E plays an essential role in chromosome movement during early mitosis and integrates mitotic spindle mechanics with regulators of the mitotic checkpoint, hence CENP-E is directly involved in coupling the mechanics of mitosis with the mitotic checkpoint signaling machinery, regulating cell-cycle transition from metaphase to anaphase. CENP-E is also essential for prometaphase chromosome movements that contribute to metaphase chromosome alignment. These processes are essential to cell proliferation. CENP-E is expressed exclusively in proliferating cells and is abundant during mitosis; it is absent from non-proliferating cells, including neurons. Inhibition of CENP-E induces cell cycle arrest in mitosis with bipolar mitotic spindles and misaligned chromosomes leading to subsequent apoptosis. GSK-923295 is the first drug candidate to enter human clinical trials that specifically targets CENP-E.