National Research Council of Canada

Chemaphor Inc.

Pharmagap Inc.

Jenny Phipps

Graham W Burton

Janusz Daroszewski

Raphael Terreux

Prabhat Arya

Compounds that are capable of inhibiting the activity of one or more protein kinases are provided. The compounds are short, predominantly basic peptidic compounds comprising between about 5 and about 20 amino acids, and can optionally comprise an ATP mimetic moiety. The protein kinase inhibiting compounds can be used to inhibit the activity of one or more protein kinases in vitro or in vivo. Also provided are methods of inhibiting a protein kinase in a subject by administration of an effective amount of a protein kinase inhibiting compound and the use of the protein kinase inhibiting compounds, alone or in combination with other chemotherapeutic agents, in the treatment of protein kinase mediated diseases and disorders. 

Inhibitors of protein kinases and uses thereof

This invention features fractionated oxidized carotenoid or retinoid mixtures, and individual components thereof, which are useful as cell-differentiation-inducing, anti-proliferative, anti-metastatic and anti-tumor agents. The mixtures and compounds of the invention can be used alone or in combination with other anticancer agents for the treatment of cancer.

Oxidized carotenoid fractions and ketoaldehyde useful as cell-differentiation inducers, cytostatic agents, and anti-tumor agents

.beta.-Carotene and canthaxanthin, as representative carotenoids, and to a lesser extent, retinoic acid, a representative retinoid, undergo extensive oxidation to yield substances, insofar as oxidized .beta.-carotene is a model, which have properties useful as non-toxic agents active against cell proliferation, tumors, and tumorigenic viruses, and useful as promoters of cell differentiation. It is evident from chemical analysis of the highly oxidized .beta.-carotene product mixture that none of the various forms of vitamin A are present or are present only in minor amounts. Furthermore, the biological activities of oxidized canthaxanthin and retinoic acid, which cannot form, vitamin A, indicate the presence of active substances that are different from vitamin A. Although the anti-proliferative and differentiation promotion activities of oxidized .beta.-carotene resemble those of vitamin A itself, generally the effects are more powerful for oxidized .beta.-carotene in a wide variety of circumstances. Unlike vitamin A, the oxidized .beta.-carotene of the invention is non-toxic.

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Chelsea, Canada

Jenny Phipps