ML199: Inhibitor of Ape1 as a Lead for Cancer Therapeutics

项目亮点：HTS筛选和药物化学优化导致一流药物，如APE1的小分子抑制剂。探针分子ML199已被交付给多个合作者，用于癌症治疗研究。目前正在进行大屏幕筛选，以确定具有改进的PK性能的有效化合物。 在此期间，NCGC与NIH和校外调查人员进行了180多次积极的合作，促进了整个人类疾病范围内的药物发现工作。这些努力已经产生了100多个高通量筛选和近60个药物化学活动，为我们的合作者和一般研究社区提供了丰富的出版物和前景光明的小分子线索。此外，NCGC还承担了一些信息学挑战，以更好地利用现有的药物和疾病目标信息，并为公众提供易于获取的资源，进一步催化人类疾病新疗法的开发。

Project highlights: HTS screening and medicinal chemistry optimization lead to a first in class drug like small molecule inhibitor of APE1. The probe molecule ML199 has been delivered to multiple collaborators to study in cancer therapy. Currently pursuing a large screen to identify potent compounds with improved PK properties. During this period, the NCGC has fostered and maintained over 180 active collaborations with both NIH and extramural investigators, facilitating drug discovery efforts across the entire spectrum of human disease. These efforts have led to over 100 high-throughput screens and nearly 60 medicinal chemistry campaigns, providing our collaborators and the general research community a wealth of publications and promising small molecule leads. In addition, the NCGC has undertaken a number of informatic challenges to make better use of existing drug and disease target information and provide the general public with easily accessible resources, further catalyzing the development of new therapies for human disease.