Work

Optimizing CRBN-ligands for optical targeted protein degradation

Year: 2026

Type: article

Abstract: , the first nanomolar photoswitchable degrader of tumor-associated protein MTH1, establishing a promising synthetic approach for future PHOTAC development. Competitive binding studies showed that irradiation lowered CRBN affinity even as degradation increased, revealing a decoupling between light-dependent changes in affinity and efficacy.

Source: RSC Medicinal Chemistry

DOI: 10.1039/d6md00266h

Authors: Joseph A. Flores, Ray G. DiNardi, George M. Burslem, Tianhao Cheng, Dirk H. Trauner

Institution: University of Pennsylvania

Language: English

Topic: Protein Degradation and Inhibitors

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Funders: National Institutes of Health, National Institute of General Medical Sciences

Awards: Structural biology and molecular biophysics training program, Optical Control of the Actin Cytoskeleton