Baranczak Aleksandra, Tu Noah P, Marjanovic Jasmina, Searle Philip A, Vasudevan Anil, Djuric Stevan W
Discovery Chemistry and Technology, AbbVie Inc., 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
ACS Med Chem Lett. 2017 Mar 28;8(4):461-465. doi: 10.1021/acsmedchemlett.7b00054. eCollection 2017 Apr 13.
The productivity of medicinal chemistry programs can be significantly increased through the introduction of automation, leading to shortened discovery cycle times. Herein, we describe a platform that consolidates synthesis, purification, quantitation, dissolution, and testing of small molecule libraries. The system was validated through the synthesis and testing of two libraries of binders of polycomb protein EED, and excellent correlation of obtained data with results generated through conventional approaches was observed. The fully automated and integrated platform enables batch-supported compound synthesis based on a broad array of chemical transformations with testing in a variety of biochemical assay formats. A library turnaround time of between 24 and 36 h was achieved, and notably, each library synthesis produces sufficient amounts of compounds for further evaluation in secondary assays thereby contributing significantly to the shortening of medicinal chemistry discovery cycles.
通过引入自动化技术，药物化学项目的生产率可显著提高，从而缩短发现周期。在此，我们描述了一个整合小分子文库合成、纯化、定量、溶解和测试的平台。该系统通过合成和测试两个多梳蛋白EED结合剂文库进行了验证，并观察到所得数据与传统方法产生的结果具有良好的相关性。这个完全自动化且集成的平台能够基于广泛的化学转化进行批量支持的化合物合成，并在多种生化检测形式中进行测试。实现了24至36小时的文库周转时间，值得注意的是，每个文库合成产生的化合物量足以用于二级检测中的进一步评估，从而为缩短药物化学发现周期做出了重大贡献。
