Compositions and methods for screening anti-cancer agents in yeast
AssigneeTufts University
InventorDean Dawson
Life of this patent
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Abstract
Methods and kits for identifying novel anti-tumor agents are provided.
Claims35
A method of identifying a compound from a library of low molecular weight compounds that activates a spindle checkpoint protein, the method comprising:
- contacting with the at least one compound a sample of a first strain of cells and a sample of a second strain of cells, wherein cells of the first strain contain a gene encoding the protein and cells of the second strain lack a gene encoding the protein in a functional form;
- and
- observing arrest of growth of the first strain of cells in comparison to the second strain of cells, and in comparison to a second sample of the first strain of cells absent the compound, the strains grown under conditions that are otherwise identical to, wherein the compound activates the spindle checkpoint.
The method according to claim 24, wherein the microtubule-destabilizing agent is selected from the group of:
- a Vinca alkaloid;
- a taxol;
- a colchicines;
- and a nocodozole.
A method of screening a plurality of compounds to identify a compound that is an antitumor agent, the method comprising:
- contacting a sample of an aneuploid strain of cells having enhanced dependence on a spindle checkpoint with the at least one compound of the plurality;
- and
- observing inhibition of growth of the aneuploid cells in comparison to a control sample of the aneuploid cells in the absence of the compound, and in comparison to a euploid strain of cells, wherein the comparison cells are grown under conditions that are otherwise identical, wherein identifying the agent that compromises the spindle checkpoint of the aneuploid cells is identifying the antitumor composition.
A kit for screening for an antitumor agent, comprising a yeast strain selected from the group of a strain having a deletion and a human replacement gene selected from the group of human genes consisting of MAD1, MAD2, MAD3, BUB1, BUBR1, and BUB3;
- at least one aneuploid strain;
- and a container and instructions for use with a plurality of compounds.
Dependencies are inferred from the claim text.