Royal College of Surgeons in Ireland
O'Dowd and Griffith ChemRxiv 23_6_2023.pdf (1.02 MB)

First-in-class metallo-PROTAC as an effective degrader of select Pt-binding proteins

Download (1.02 MB)

The targeted degradation of proteins bound by metals represents a promising approach to treat diseases. We report the development of the first metallo-PROTAC, specifically a Pt-PROTAC, that can effectively degrade select Pt(II)-binding proteins. The reported Pt-PROTAC prototype successfully degraded thioredoxin-1 and thioredoxin reductase-1 though not glutathione-S-transferase in JJN3 and MM1.S multiple myeloma cancer cell lines. Deactivated Pt-PROTAC does not degrade thioredoxin-1 and thioredoxin reductase-1. Furthermore pretreatment of cells with the proteasome inhibitor bortezomib prevents Pt-PROTAC target degradation thereby implicating the ubiquitin proteasome system with its mode of degradation. Metallo-PROTACS will have important applications in the identification of metal binding proteins and as chemotherapeutic agents. 


Synthesis and Solid State Pharmaceutical Centre (SSPC)

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



The original article is available at Published version is available at Published version is available in Chem Commun (Camb) and RCSI repository

Published Citation

O'Dowd P, Sullivan G, Rodrigues D, Ní Chonghaile T, Griffith D. First-in-class metallo-PROTAC as an effective degrader of select Pt-binding proteins. ChemRxiv. Cambridge: Cambridge Open Engage; 2023

Publication Date

26 Jun 2023


  • Chemistry
  • Physiology and Medical Physics
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Cancer
  • Chemistry and Pharmaceutical Sciences


Cambridge Open Engage


  • Submitted Version (Preprint)