Reynders M,
Matsuura BS,
Bérouti M,
Simoneschi D,
Marzio A,
Pagano M.
*
Trauner D.
* New York University, USA
PHOTACs Enable Optical Control of Protein Degradation.
Sci. Adv. 2020;
6
DOI:
10.1126/sciadv.aay5064
Key words
PHOTACs - photopharmacology - PROTACs
Significance
PROTACs (PROteolysis TArgeting Chimeras) have emerged as a new modality in pharmacology
(Sakamoto et al. PNAS 2001, 98, 8554), but their catalytic mechanism of action poses risks. PHOTACs (PHOtochemically
TArgeting Chimeras) can be spatiotemporally controlled for precise and reversible
switching between active and inactive states using light.
Comment
Based on a photoswitchable analog of the cereblon ligand thalidomide, this approach
provides a general method to turn PROTACs into PHOTACs, which are active only upon
irradiation. The authors use this strategy for the targeted degradation of BRD2/3/4
and FKBP12.
