Method for screening compounds that selectively interact with rad9

Abstract

Natural and synthetic compounds of Formulae Ia-Ie having a lactone structure, in particular Securolide, have been determined to be effective anti-tumor compounds which target the hrad9 gene and/or protein encoded thereby or complex containing the protein and/or the p53 gene and/or protein. Securolide is cytoselective for mutants of hRad9 based on studies conducted in Rad9 mutant yeast strains. Securolide appears to interact with mutant hRad9 in cancer cells to produce DNA lesions which result in apoptosis. Studies have demonstrated that Securolide is useful for treating proliferation disorders such as melanoma, leukemia, breast cancer, lung cancer, ovarian cancer, colon cancer, esophagus cancer, liver cancer, and lymphatic cancer, and to alleviate pain associated with the cancer. Other compounds effective for the treatment of cancer and optionally pain associated therewith may also be identified using the same assays, for example, by screening for efficacy in assays using Rad9 and/or p53 defective mutant yeasts.

Description

technical field [0001] The present invention is generally in the field of targeting anticancer compounds and methods for their screening. [0002] Cross References to Related Applications [0003] This application claims U.S.S.N.61 / 108,224, "Method for Screening for Compounds Selectively Interacting with RAD9" filed on October 24, 2008 by David Terrero, "Method for Screening for Compounds Selectively Interacting with RAD9 )” priority. Background technique [0004] Many compounds are known to treat cancer. In general, most of the compounds work by inhibiting DNA replication or cell proliferation, but are not specific to transformed cells. Although specificity has been conferred on tumor cells through the use of targeting ligands and binding to specific receptors, most antineoplastic compounds generally work by killing more rapidly proliferating tumor cells than slower replicating normal cells . [0005] There is a need for highly selective compounds that are cytotoxic t...

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Problems solved by technology

Although specificity has been conferred on tumor cells through the use of targeting ligands and binding to specific receptors, mo

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