Identification of Inhibitors of human Lactate Dehydrogenase A (LDHA) as Anti-cancer Agents

项目要点：筛选了完整的化合物文库，并确定了要开发的铅化学类型。药物化学正在提高LDHA抑制活性，一系列先进的分析正在进行中，以表征这些化合物的细胞活性，并支持领先候选化合物的临床前进展。 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: the full compound library was screened and a lead chemotype was identified for development. Medicinal chemistry is ongoing to improve LDHA inhibitory activity, and a battery of advanced assays are in progress to characterize cellular activity of these compounds and support preclinical advancement of a lead candidate. 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.