Accelerating PROTACs Discovery Through a Direct-to-Biology Platform Enabled by Modular Photoclick Chemistry.

ABSTRACT: Proteolysis targeting chimeras (PROTACs) have emerged as a promising strategy for drug discovery and exploring protein functions, offering a revolutionary therapeutic modality. Currently, the predominant approach to PROTACs discovery mainly relies on an empirical design-synthesis-evaluation process involving numerous cycles of labor-intensive synthesis-purification and bioassay data collection. Therefore, the development of innovative methods to expedite PROTAC synthesis and exploration of chemical space remains highly desired. Here, a direct-to-biology strategy is reported to streamline the synthesis of PROTAC libraries on plates, enabling the seamless transfer of reaction products to cell-based bioassays without the need for additional purification. By integrating amide coupling and ligh

SUBMITTER: Yan KN 

PROVIDER: S-EPMC11234393 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature