We report the development of the first metallo-PROTAC, specifically a Pt-PROTAC, that can effectively degrade select Pt(II)-binding proteins. The Pt-PROTAC prototype successfully degraded thioredoxin-1 and thioredoxin reductase-1 in multiple myeloma cancer cell lines. Metallo-PROTACs will have important applications in the identification of metal binding proteins and as chemotherapeutic agents.
Funding
SSPC PharM5 | Funder: Science Foundation Ireland | Grant ID: 12/RC/2275_P2
Irish Research Council (IRCLA/ 2022/2822)
SFI (19/FFP/646)
Irish Research Council (GOIPD/2022/764)
Irish Cancer Society under grant number CRF21SUL
European Regional Development Fund under Grant Number 12/RC/2275_P2
History
Comments
The original article is available at https://pubs.rsc.org/
Pre-print is available on ChemRxiv. https://doi.org/10.26434/chemrxiv-2023-r5l4k and RCSI Repository https://hdl.handle.net/10779/rcsi.24204363.v1
Published Citation
O'Dowd PD, Sullivan GP, Rodrigues DA, Chonghaile TN, Griffith DM. First-in-class metallo-PROTAC as an effective degrader of select Pt-binding proteins. Chem Commun (Camb). 2023;59(84):12641-12644.