Click. Screen. Degrade. A Miniaturized D2B Workflow for Rapid PROTAC Discovery.

ABSTRACT: Targeted protein degradation is one of the fastest developing fields in medicinal chemistry and chemical biology. Despite significant development in assay technologies and inhibitor discovery, the development of PROTACs remains a challenging endeavor since rational design approaches remain widely elusive. Our workflow eliminates the rate-limiting step of classic synthesis, namely compound purification, and pairs it with high-throughput, semi-automated plate-based synthesis, and direct cellular assay evaluation. We applied this direct-to-biology approach to four diverse targets, demonstrating the general applicability of this technology. PROTAC synthesis was realized by using the highly efficient copper-catalyzed azide-alkyne cycloaddition reaction. This simplified reaction setup enabled sy

SUBMITTER: Mitrovic M 

PROVIDER: S-EPMC12910640 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature