Small molecules that induce protein degradation through ligase-mediated ubiquitination, have shown considerable promise as a new pharmacological modality. Thalidomide and related IMiDs provided the clinical proof of concept, while significant progress has recently been made towards chemically induced targeted protein degradation using heterobifunctional small molecule ligands. We will present recent work towards a better understanding of the molecular principles that govern neo-substrate recruitment, and other small molecule degraders.

Principles of small molecule mediateed ubiquitin ligase targeting

2019 Fall National Meeting

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