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• W2912071003 abstract "The Ras–Raf–MEK1/2–ERK1/2 pathway is an attractive target for the development of anticancer agents because of the high prevalence of ERK activation in human cancers. However, resistance is often developed despite initial clinical response, most likely because of activation of cross-talk pathways. In Research Genetic Cancer Center (RGCC), we are in the process of synthesizing a novel ERK inhibitor, targeting the final stage of the pathway, thus minimizing cross-talk. We have synthesized an intermediate molecule –RGCC416 – and tested its biological activity. MCF-7 and MDA-MB-231 cells were used. Cell viability was measured by crystal violet and cell proliferation by the methyl tetrazolium assay using various compound concentrations. Cell migration and colony formation were determined to assess the ability of invasion and single cancer cell growth, respectively. Expression of genes linked to MAPK/PI3K pathways was determined by PCR. ERK and phospho-ERK levels were determined in both the cytoplasm and the nucleus by western blot. It was found that although the compound did not affect viability, it significantly decreased cell proliferation, migration, and colony formation in both cell lines. In MDA-MB-231, this is possibly through retaining phospho-ERK to the cytoplasm, where it cannot activate cancer-associated genes. There was no difference in ERK levels in MCF-7 cells. This could be because of the different pathways that these cells utilize for survival. We have synthesized a molecule, which could be a promising ERK inhibitor, leading to possible novel treatment options for breast cancer patients." @default.
• W2912071003 created "2019-02-21" @default.
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• W2912071003 date "2019-07-01" @default.
• W2912071003 modified "2023-09-25" @default.
• W2912071003 title "Novel small molecule decreases cell proliferation, migration, clone formation, and gene expression through ERK inhibition in MCF-7 and MDA-MB-231 breast cancer cell lines" @default.
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• W2912071003 doi "https://doi.org/10.1097/cad.0000000000000766" @default.
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