Product name
Poloxin: a polo-like kinase PBD small molecule inhibitor from Max-Planck-InnovationSummary
The first small molecule and non-peptidic inhibitor of the Plk1 polo-box domainOrganization name
Max-Planck-Innovation GmbHProfile
The serine/threonine kinase Plk1 is overexpressed in many types of human cancers, and has been implicated as an adverse prognostic marker for cancer patients. Its inhibition in cancer cells by targeting its catalytic activity has been uniformly demonstrated to induce mitotic arrest and apoptosis of cancer cells in vitro and in vivo. Inhibition of Plk1 by small-molecule inhibitors of its catalytic activity is currently being explored in clinical settings.
Plk1 localizes to its intracellular anchoring sites via its polo-box domain (PBD). Since the PBD is unique to the family of Plks and is essential for Plk functions, the PBD is ideally suited to the exploration of the feasibility of inhibiting a serine/threonine kinase by interfering with its intracellular localization, rather than targeting the conserved ATP-binding site. Moreover, small-molecules targeting the PBD should be useful research tools to decipher the biological role of the Plk1 PBD in mammalian cells.
Technology
The technology discloses the first nonpeptidic inhibitors of the Plk1 PBD. The natural product Thymoquinone and its synthetic derivative Poloxin were found to inhibit the functions of the Plk1 PBD in vitro and in HeLa cells. Plk1 can be inhibited by small molecules which interfere with its intracellular localization by inhibiting the function of the PBD. The natural product Thymoquinone and especially, the synthetic Thymoquinone derivative Poloxin are the first known inhibitors of the Plk1 PBD. Both compounds inhibit the function of the Plk1 PBD in vitro, and cause Plk1 mislocalization, chromosome congression defects, mitotic arrest, and apoptosis in HeLa cells. The data validate the Plk1 PBD as anti-cancer target and provide a rationale for developing thymoquinone derivatives as anti-cancer drugs.
Commercial Opportunity
In-licensing or collaboration partnership for further development.
Patent Situation
A European patent application was filed in September 2007.
Contact
Max-Planck-Innovation GmbH
Dr. Matthias Stein-Gerlach
stein-gerlach(at)max-planck-innovation.de
About Max-Planck-Innovation GmbH
Max Planck Innovation advises and supports scientists of the Max Planck Society in evaluating inventions and filing patent applications. They market patents and technologies to industry and coach founders of new companies based on research results from Max Planck Institutes. Every year, they evaluate about 130 inventions, of which 80 to 100 lead to the filing of a patent. In the last five years alone, they advised 28 spin-offs, closed more than 450 license deals and generated proceeds of more than €100m for inventors, institutes and the Max Planck Society. As a result, Max Planck Innovation is among the world's most successful technology transfer organizations. Max Planck Innovation was founded in 1970 as Garching Instrumente GmbH and operated under the name of Garching Innovation from 1993 to 2006.
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