High throughput screen (HTS) to identify chemotherapeutic compounds by interfering with cell cycle checkpoint functions

摘要

The present invention relates to a method for the identification of synergistic compounds which act synergistically with compounds blocking DNA replication for e.g. the treatment of cancer, said method comprising the steps of a) incubating a compound of interest with a mutant yeast strain, wherein said mutant yeast strain is deficient for an orthologue of a human protein involved in check point control, and wherein the growth medium of said mutant yeast strain comprises a compound blocking DNA replication at a concentration which is non-toxic for said mutant yeast strain, and b) incubating said compound of interest with the corresponding wild type yeast strain of the mutant yeast strain of step a), wherein the growth medium of said wild-type yeast strain comprises a compound blocking DNA replication at a concentration which is non-toxic for said wild-type yeast strain, wherein a compound of interest which inhibits the growth of said mutant yeast strain in the presence of a compound blocking DNA replication at a concentration which is non-toxic for said mutant yeast strain, but does not inhibit the growth of the corresponding wild-type yeast strain in the presence of a compound blocking DNA replication at a concentration which is non-toxic for said wild type-yeast strain is a synergistic compounds which act synergistically with compounds blocking DNA replication for e.g. the treatment of cancer.