Discovery of inhibitors of BK polyomavirus

项目摘要 BK多瘤病毒（BKPyV）的新型抑制剂是目前急需的，以防止病毒诱导的肿瘤坏死因子（TNF）的发生。 肾病、同种异体移植物衰竭和移植后出血性膀胱炎。本SBIR第I阶段的目标 可行性研究是鉴定特异性抑制BKPyV复制的药物样化合物。在此过程中， 在第一阶段的资助期间，我们将执行一项命中发现活动，其中包含100，000种具有最佳药物样活性的化合物库。 特性.将对试验中出现的质量命中进行后续检测，以研究效价， 选择性和作用机制。这些化合物中最令人感兴趣的将进行药物化学研究 驱动的命中到领导的努力，探索结构-活性关系（SAR）。这个项目的总体目标是发现一个 或更多新的先导系列，其被定义为表现出易处理的SAR、有效的抗病毒 对可用的BKPyV菌株的活性和最小的细胞毒性。这些努力的成功将触发 提交第二阶段申请，将项目从早期潜在客户优化阶段推进到候选阶段 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.