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YU 238259 is a novel DNA double-strand break repair inhibitor that exhibits potent synthetic lethality in the setting of DNA damage response and DNA repair defects; specifically inhibits homology-dependent DNA repair (HDR), but not non-homologous end-joining (NHEJ), in cell-based GFP reporter assays; significantly delays tumor growth of BRCA2-deficient human tumor xenografts in nude mice.




HUHS-015 (HUHS015) is a potent, orally active prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitor with IC50 of 0.67 uM; significantly suppresses the growth of DU145 cells in vitro and in a mouse xenograft model.




ML216 (CID49852229) is a potent, selective inhibitor of DNA unwinding activity of BLM (Bloom's syndrome protein) with IC50 of 2.98 and 0.97 uM for full length BLM and BLM636-1298, respectively; weak inhibits WRN helicase (IC50=12.6 uM) and does not inhibit RecQ1, RecQ5 and UrvD (IC50>50 uM); disrupts BLM’s binding to DNA, rather than being an inhibitor of ATP binding by BLM, the inhibition of ssDNA-dependent ATPase activity with Ki of 1.76 uM, shows cell-based activity and can induce sister chromatid exchanges, enhances the toxicity of aphidicolin, and exerts antiproliferative activity in cells expressing BLM.




AOH1160 (AOH-1160) is a potent, first-in-class, orally available small molecule inhibitor of Proliferating cell nuclear antigen (PCNA); selectively kills many types of cancer cells at below micromolar concentrations (mean GI50=330 nM) without causing significant toxicity to a broad range of non-malignant cells, interferes with DNA replication, blocks homologous recombination-mediated DNA repair, and causes cell cycle arrest; suppresses tumor growth without causing significant side effects in mice, demostrates the potential as a broad-spectrum therapeutic agent for cancer treatment.




A12B4C3 (hPNKP inhibitor A12B4C3) is a specific, noncompetitive inhibitor of the human DNA repair enzyme polynucleotide kinase/phosphatase (hPNKP) with C50 of 60 nM, displays no inhibition of calcineurin and protein phosphatase-1 or APTX; A12B4C3 enhanced the radiosensitivity of human A549 lung carcinoma and MDA-MB-231 breast adenocarcinoma cells, failed to increase the radiosensitivity of the hPNKP-depleted cells; A12B4C3 also inhibits the repair of DNA single and double strand breaks following exposure of cells to ionizing radiation, but does not inhibit two other key strand-break repair enzymes, DNA polymerase beta or DNA ligase III,

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