Identifying novel antibiotics by targeting the EF-Tu complex formation

在NCATS，我们启动了在全自动平台qHTS机器人系统上采用1536孔格式建立factumycin、kirromycin和GE2270A的试剂稳定性和剂量响应曲线的检测方案。我们测试了不同的平板阅读器，即Envision、ViewLux和PHERAstar，以确认阅读器特别适用于该分析，看起来Envision是未来平板阅读器的首选。NCATS团队对1280个化合物的LOPAC文库进行了离线和在线两种模式的初步筛选。确定了五个阳性命中。对这些化合物进行二次筛选，以确认筛选结果，发现其中一种化合物具有良好的抗生素活性。目前正在对这一已证实的靶向分子进行药代动力学研究，并对类似物进行评价。

At NCATS, we initiated work on establishing the assay protocol on fully automated platform qHTS robotic system using 1536 well format in terms of reagent stability and dose response curve of factumycin, kirromycin and GE2270A. Different plate readers namely Envision, ViewLux and PHERAstar were tested to confirm the suitability of the reader specifically for this assay and it seems Envision is the plate reader of choice moving forward. Initial screening of LOPAC library of 1280 compounds was performed in offline as well as online mode by NCATS team.Five positive hits were identified. Secondary screening of these compounds, to confirm the screening outcome, disclosed that one of them display good antibiotic activity. Pharmacokinetic studies of this confirmed hit molecule and evaluation of analogues are going.