GlaxoSmithKline extends Cytokinetics cancer collaboration

By Wai Lang Chu

- Last updated on GMT

Related tags: Cell cycle

GlaxosmithKline (GSK) has agreed to continue its collaboration with
CytoKinetics, which focused towards the mitotic kinesin,
centromere-associated protein E (CENP-E) that has evolved to become
a novel and viable drug target.

The extension builds on the relationship formed in June 2001, which served to investigate the feasibility of novel small molecule therapeutics targeting mitotic kinesins for applications in the treatment of cancer and other diseases.

The alliance proved successful generating two drug candidates in clinical development, ispinesib and SB-743921, and one potential drug candidate in preclinical development, GSK-923295.

Anti-mitotic drugs (taxanes and vinca alkaloids) have advanced the treatment of cancer and are commonly used for the treatment of several tumour types.

However, these drugs have demonstrated limited treatment benefit against certain cancers. In addition, these drugs target tubulin, a cytoskeletal protein involved not only in mitosis and cell proliferation, but also in other important cellular functions.

Mitotic kinesins are essential to mitosis, and, unlike tubulin, appear to have no role in unrelated cellular functions. The drug candidates that inhibit kinesin spindle protein (KSP) and CENP-E and other mitotic kinesins may represent the next generation of anti-mitotic cancer drugs by arresting mitosis and cell proliferation without impacting unrelated, normal cellular functions, thereby avoiding many of the toxicities commonly experienced by patients treated with existing anti-mitotic drugs.

During this research extension of one year, both companies will continue to perform research activities focused to translational research directed towards CENP-E.

CENP-E is a mitotic kinesin directly involved in coupling the mechanics of mitosis with the mitotic checkpoint signaling machinery, regulating cell-cycle transition from metaphase to anaphase.

In September 2005, Cytokinetics and GSK announced an amendment to their original agreement to provide Cytokinetics an expanded role in the clinical research and development of SB-743921.

Under the terms of this agreement Cytokinetics funded development activities to explore the application of SB-743921 for the treatment of non-Hodgkin's lymphoma, Hodgkin's lymphoma and multiple myeloma,

GSK had the option of resuming responsibility for development and commercialisation activities for SB- 743921 for these indications during a defined period.

CENP-E is also essential for prometaphase chromosome movements that contribute to metaphase chromosome alignment. These processes are essential to cell proliferation. Preventing cell proliferation by disrupting mitosis is a validated approach to treating patients with cancer.

We are pleased to extend our collaborative research with GlaxoSmithKline,"​said Robert Blum, President, Cytokinetics.

I believe that translational research specifically focused towards CENP-E could be helpful in support of preclinical development activities for GSK-923295 and the expected movement of this novel compound into human clinical trials next year,"​added.

CENP-E is a mitotic kinesin 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.

Preventing cell proliferation by disrupting mitosis is a validated approach to treating patients with cancer.

Current anti-mitotic drugs such as the taxanes and vinca alkaloids, have demonstrated drawbacks as they target proteins involved in other important cellular functions.

Inhibition of these other cellular functions produces dose- limiting toxicities such as peripheral neuropathy, an impairment of the peripheral nervous system.

Neuropathies are thought to result when these drugs interfere with the dynamics of microtubule filaments that are responsible for the long-distance transport of important cellular components within nerve cells.

Related topics: Preclinical Research, GlaxoSmithKline

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