Taylor Christopher E, Pan Quintin, Mapp Anna K
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
ACS Med Chem Lett. 2012 Jan 12;3(1):30-34. doi: 10.1021/ml200186r.
In spite of their considerable therapeutic potential, the development of highly potent and selective transcriptional inhibitors has proven elusive. We demonstrate that combinations of transcriptional inhibitors of erbB2 expression and existing therapeutic agents that target erbB2 activity and lifetime lead to a synergistic increase in activity, with dose reductions as high 30 fold compared to individual agents. The synergy is selective for erbB2 overexpressing cancer cells. These results highlight the potential of a generalizable approach that will improve the utility of transcriptional inhibitors as both biochemical tools and potential therapeutics.
尽管具有相当大的治疗潜力，但高效且选择性的转录抑制剂的开发一直难以实现。我们证明，erbB2表达的转录抑制剂与靶向erbB2活性和寿命的现有治疗药物联合使用，可导致活性协同增加，与单一药物相比，剂量降低高达30倍。这种协同作用对erbB2过表达的癌细胞具有选择性。这些结果突出了一种可推广方法的潜力，该方法将提高转录抑制剂作为生化工具和潜在治疗药物的效用。
