- Tetrazole-Based Probes for Integrated Phenotypic Screening, Affinity-Based Proteome Profiling, and Sensitive Detection of a Cancer Biomarker
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Target-identification phenotypic screening has been a powerful approach in drug discovery; however, it is hindered by difficulties in identifying the underlying cellular targets. To address this challenge, we have combined phenotypic screening of a fully functionalized small-molecule library with competitive affinity-based proteome profiling to map and functionally characterize the targets of screening hits. Using this approach, we identified ANXA2, PDIA3/4, FLAD1, and NOS2 as primary cellular targets of two bioactive molecules that inhibit cancer cell proliferation. We further demonstrated that a panel of probes can label and/or image annexin A2 (a cancer biomarker) from different cancer cell lines, thus providing opportunities for potential cancer diagnosis and therapy.
- Cheng, Ke,Lee, Jun-Seok,Hao, Piliang,Yao, Shao Q.,Ding, Ke,Li, Zhengqiu
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