DARTS ：药物亲和反应靶向稳定性技术服务

|   技术路线

|   技术优势

|   经典案例：DARTS结合cMAP技术发现水仙环素抗乳腺癌直接靶点STAT3

研究人员首先利用cMAP分析技术筛选出与水仙环素Narciclasine (Nar) 具有类似功能的化合物，分析这些化合物调控的基因表达谱，发现它们在细胞增殖相关通路中富集度最为显著，而STAT3作为明星转录因子，在多种肿瘤的细胞增殖过程中起到关键调控作用。研究人员预测Nar可能通过抑制STAT3等细胞增殖基因发挥其抗肿瘤活性。进一步，通过DARTS技术，研究人员发现Nar确实能够结合STAT3蛋白，该结论并得到微量热泳动MST等技术的证实。

接下来，通过luciferase荧光素酶等一系列分子实验，研究人员确定了Nar是通过直接与 STAT3的SH2 结构域结合来抑制 STAT3 的磷酸化激活、二聚化以及核转位，阻止其入核发挥转录因子作用去促细胞增殖基因表达，最终起到了抗肿瘤效应。同时，Nar的抗肿瘤作用在选择性雌激素受体调节剂他莫昔芬耐药的乳腺癌MCF-7细胞株中得到证实，说明Nar可能是雌激素受体依赖性乳腺癌耐药人群新的潜在治疗药物。

|   参考文献

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