Identification of small molecule inhibitors of USP15

鉴于USP15在肿瘤发生和T细胞活化中的作用，USP15是癌症和癌症免疫治疗的有希望的靶标。通过定量高通量筛选和进一步开发先导化合物来鉴定USP15特异性小分子抑制剂，不仅可以开辟治疗癌症的新策略，还可以更好地了解USP15的生物学功能。在此期间，项目团队致力于验证先前完成的高通量筛选中的小分子命中。使用针对筛选命中测试的正交试验的活性特征，该团队采用机器学习方法对另外100，000个小分子进行计算机筛选，以扩大对USP 15具有抑制活性的前瞻性化学型的数量。

Given USP15s role in tumorigenesis and T cell activation, USP15 is a promising target for cancer and cancer immunotherapy. Identification of USP15-specific small-molecule inhibitors through a quantitative high-throughput screening and further development of the lead compound could not only open new strategies to tackle cancer, but allow to better understand biological functions of USP15. During this period, the project team worked to validate small molecule hits from the previously completed high-throughput screen. Using activity profiles from the orthogonal assays tested against the screening hits, the team employed a machine learning approach to conduct an in silico screen against an additional 100,000 small molecules to extend the number of prospective chemotypes with inhibitory activity against USP15.