德孚医药出版社专门从事开放获取同行评议期刊的出版业务,这些期刊广泛地涉及科学、技术特别是医药领域。德孚旗下共有 130 多种开放获取期刊，许多优秀医药论文已经在我们的中文网站上发表。我们特意摘选了一些论文，与大家一起分享：

进入表皮生长因子受体（HER）家族的蛋白激酶的结合口袋: 新型 EGFR 抑制剂被发现可作为抗肿瘤剂

The epidermal growth factor receptor (EGFR) family has been validated as a successful antitumor drug target for decades. Known EGFR inhibitors were exposed to distinct drug resistance against the various EGFR mutants within non-small-cell lung cancer (NSCLC), particularly the T790M mutation. Although so far a number of studies have been reported on the development of third-generation EGFR inhibitors for overcoming the resistance issue, the design procedure largely depends on the intuition of medicinal chemists.

Here we retrospectively make a detailed analysis of the 42 EGFR family protein crystal complexes deposited in the Protein Data Bank (PDB). Based on the analysis of inhibitor binding modes in the kinase catalytic cleft, we identified a potent EGFR inhibitor (compound A-10) against drug-resistant EGFR through fragment-based drug design. This compound showed at least 30-fold more potency against EGFR T790M than the two control molecules erlotinib and gefitinib in vitro.

Moreover, it could exhibit potent HER2 inhibitory activities as well as tumor growth inhibitory activity. Molecular docking studies revealed a structural basis for the increased potency and mutant selectivity of this compound. Compound A-10 may be selected as a promising candidate in further preclinical studies. In addition, our findings could provide a powerful strategy to identify novel selective kinase inhibitors on the basis of detailed kinase–ligand interaction space in the PDB.

磁性丝素蛋白纳米粒用于按摩式经皮给药的研究

本文对联合磁性纳米粒及交变磁场协同促进药物经皮渗透进行了研究。首先，利用超临界强制分散悬浮液法制备甲氨喋呤-丝素蛋白磁性纳米粒，并对其物化性能进行表征。其次，对不同磁场作用及被动扩散下的体外经皮给药实验进行了比较研究，实验结果发现，相较于被动扩散，固定磁场作用下的药物增渗因子提高；相较于固定磁场，交变磁场能更有效地促进药物的经皮渗透；而联合固定磁场及交变磁场能够对皮肤产生按摩效果，使增渗效果最好。

最后，对于机理研究，通过傅立叶变换衰减全反射红外光谱测试显示交变磁场能够改变角质层脂质的有序排列，从而增加了角质层脂质的流动性，促进药物经皮渗透；通过共聚焦激光扫描显微镜观察荧光在皮肤中的分布，结果表明，与其他实验组相比，联合固定及交变磁场作用下皮肤深处观察到较大区域的荧光信号，表明模拟按摩能够通过增加毛囊渗透途径促进药物经皮渗透。联合磁性纳米粒及固定/交变磁场有望应用于按摩式经皮给药传递。

培美曲塞单药与联合用药方案治疗晚期非小细胞肺癌的对比:一项最新的 Meta 分析

目前培美曲塞已经作为晚期非小细胞肺癌患者二线治疗的推荐用药，然而培美曲塞联合用药是否提高治疗疗效及安全性尚有争议。因此本研究进行了一项 Meta 分析解决这一争议。 研究人员用计算机检索 PubMed、Embase 以及 the Cochrane Central Register of Controlled Trials，检索日期截止 2015 年 4 月份。合并的风险比(HRs)和 95% 可信区间(CIs)用来评估总生存期(OS)及无进展生存期(PFS)；合并的优势比(ORs)和 95% 可信区间(CIs)用来评估总反应率(ORR)及大于等于 3 级的毒性反应。另外，亚组分析，敏感性分析及发表偏倚也进行了评估。