Method for screening compounds that selectively interact with rad9
A technology of compounds and complexes, applied in the fields of biochemical equipment and methods, determination/inspection of microorganisms, drug combinations, etc.
Inactive Publication Date: 2011-11-30
MAGNACHEM INT LAB
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Although specificity has been conferred on tumor cells through the use of targeting ligands and binding to specific receptors, mo
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example 1
[0085] Example 1: Bioanalysis on Saccharomyces cerevisiae using Secroder
[0086] Cycloderm (LMSV-6) at concentrations between 10 μg / ml and 100 μg / ml on solid medium against a panel of S. cerevisiae mutant strains whose DNA is similar to that found in tumors / cancer cells biological analysis. Cycloderm showed significant cytotoxic activity only against mutant strains, especially the gene rad9. This suggests that Secroderma is selectively cytotoxic to cells with unstable genomes.
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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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IPC IPC(8): G01N33/50
CPCG01N2510/00G01N2333/4739G01N33/5011C12Q1/18A61P35/00G01N33/15G01N33/50C12Q1/04
Inventor 大卫·特雷罗费德里科·M·戈麦斯C·费德里科·戈麦斯·加西亚-戈多伊
Owner MAGNACHEM INT LAB
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