演題：Systematic Targeting of Protein Complexes with Molecular COUPLrs

演者：Liron Bar-Peled
　　　(Principal Investigator, Massachusetts General Hospital Cancer Center,

          Associate Professor, Department of Medicine, Harvard Medical School)

抄録：
Small molecules that modulate protein complexes have reshaped cell biology and driven advances in clinical oncology, yet their discovery remains largely serendipitous. To overcome this challenge, we developed molecular COUPLrs, elaborated small molecules flanked by two cysteine-reactive warheads, as well as CONNECT, an integrated chemical proteomic platform for target deconvolution. By profiling a library of molecular COUPLrs across 13 cancer cell lines, we uncovered hundreds of proteins that can be coupled together, including mutant selective complexes.  We develop an advanced COUPLr for the oncogene EML4-ALK, which engages the fusion outside of its kinase domain, restricts protein dynamics, and disrupts EML4-ALK signaling. Interestingly, COUPLr binding leads to EML4-ALK degradation–a characteristic shared with ALK-directed drugs we converted into COUPLrs. Collectively, molecular COUPLrs provide an unbiased approach to identify small molecules that target protein complexes. 

日　時：2025年12月9日（火）15：00 〜 16：00
場　所：セミナー室B