Discovery of inhibitors of BK polyomavirus

项目总结 迫切需要新的BK多瘤病毒(BK)抑制剂来预防病毒诱导的BK多瘤病毒的发生 移植后肾病、同种异体移植失败和出血性膀胱炎。第一阶段SBIR的目标是 可行性研究是确定特定抑制BKPyV复制的类药物化合物。在这个过程中 在第一阶段资助期内，我们将通过一个包含100,000种具有最佳药物性质的化合物的库来执行一项热门搜索活动 属性。从化验中产生的高质量命中将接受后续测试，以调查其效力， 选择性和作用机理。其中最有趣的化合物将受到药物化学的影响 推动了探索结构-活性关系(SAR)的点击到主导的努力。这个项目的总体目标是发现一个 或更新的铅系列，其定义为一种化学型抑制剂，显示出易处理的SAR，有效的抗病毒 对现有BKPyV毒株的活性和最小的细胞毒性。这些努力的成功将引发 提交第二阶段申请，将计划从早期的潜在客户优化提升到候选人 选择。

PROJECT SUMMARY Novel inhibitors of BK polyomavirus (BKPyV) are urgently needed to prevent the occurrence of virus-induced nephropathy, allograft failure and hemorrhagic cystitis following transplantation. The objective of this Phase I SBIR feasibility study is to identify drug-like compounds that specifically inhibit BKPyV replication. During the course of this Phase I funding period, we will execute a hit finding campaign with a library of 100,000 compounds with optimal drug-like properties. Quality hits that emerge from the assay will be subjected to follow-on testing that will investigate the potency, selectivity, and mechanism of action. The most interesting of these compounds will be subjected to medicinal chemistry driven hit-to-lead efforts to explore structure-activity relationships (SAR). The overall goal of this project is to discover one or more novel lead series, which is defined as a chemotype inhibitor that demonstrates tractable SAR, potent antiviral activity against the available BKPyV strains and minimal cytotoxicity. Success in these endeavors will trigger the submission of a Phase II application that will advance the program from Early Lead Optimization through to Candidate Selection.