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

Paul D O'Dowd; Graeme P Sullivan; Daniel A Rodrigues; Tríona Ní Chonghaile; Darren M Griffith

doi:10.1039/d3cc03340f

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

Chem Commun (Camb). 2023 Oct 19;59(84):12641-12644. doi: 10.1039/d3cc03340f.

Authors

Paul D O'Dowd^{1

2}, Graeme P Sullivan³, Daniel A Rodrigues¹, Tríona Ní Chonghaile³, Darren M Griffith^{1

2}

Affiliations

¹ Department of Chemistry, Royal College of Surgeons in Ireland, Dublin 2, Ireland. dgriffith@rcsi.ie.
² SSPC, the Science Foundation Ireland Research Centre for Pharmaceuticals, Ireland.
³ Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.

PMID: 37791917
DOI: 10.1039/d3cc03340f

Abstract

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.

MeSH terms

Carrier Proteins*
Humans
Neoplasms*
Proteins
Proteolysis

Substances

Carrier Proteins
Proteins