英国爱丁堡大学23日发布一项研究成果介绍说，该校研究人员领衔的团队找到一种化合物，它能在实验室环境中有效抑制乳腺癌细胞的生长。科学家有望基于这一发现开发出新一代乳腺癌治疗药物。

据研究人员介绍，他们利用一种先进的成像技术，能够将化合物作用于癌细胞的过程可视化。在这种技术的辅助下，研究人员筛选出名为“eCF506”的化合物，它能够针对乳腺癌细胞生长和扩散的关键分子“Src酪氨酸激酶”发挥作用。

目前已有其他一些进入临床试验阶段的新药可作用于“Src酪氨酸激酶”分子。与这些药物相比，“eCF506”的一个很大优势是针对性更强，只会作用于“Src酪氨酸激酶”，而不会影响细胞中其他分子。从理论上说，它作为药物效果更强，副作用也更低。

这项研究已发表在《医学化学杂志》上。参与研究的爱丁堡大学教授尼尔·卡拉格说，这一候选药物还需要经过更多的前期测试才能进入临床试验阶段，但从目前的情况看，它的效果非常不错。（来源：新华社 张家伟）

Rapid Discovery and Structure–Activity Relationships of Pyrazolopyrimidines That Potently Suppress Breast Cancer Cell Growth via SRC Kinase Inhibition with Exceptional Selectivity over ABL Kinase

Abstract  Novel pyrazolopyrimidines displaying high potency and selectivity toward SRC family kinases have been developed by combining ligand-based design and phenotypic screening in an iterative manner. Compounds were derived from the promiscuous kinase inhibitor PP1 to search for analogs that could potentially target a broad spectrum of kinases involved in cancer. Phenotypic screening against MCF7 mammary adenocarcinoma cells generated target-agnostic structure–activity relationships that biased subsequent designs toward breast cancer treatment rather than to a particular target. This strategy led to the discovery of two potent antiproliferative leads with phenotypically distinct anticancer mode of actions. Kinase profiling and further optimization resulted in eCF506, the first small molecule with subnanomolar IC50 for SRC that requires 3 orders of magnitude greater concentration to inhibit ABL. eCF506 exhibits excellent water solubility, an optimal DMPK profile and oral bioavailability, halts SRC-associated neuromast migration in zebrafish embryos without inducing life-threatening heart defects, and inhibits SRC phosphorylation in tumor xenografts in mice.

原文链接：http://pubs.acs.org/doi/pdf/10.1021/acs.jmedchem.6b00065