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

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

Paul D. O’Dowd,

^ab Graeme P. Sullivan,^c Daniel A. Rodrigues,^a Tríona Ní Chonghaile^c and Darren M. Griffith

*^ab

Author affiliations

* Corresponding authors

^a Department of Chemistry, Royal College of Surgeons in Ireland, Dublin 2, Ireland
E-mail: dgriffith@rcsi.ie

^b SSPC, the Science Foundation Ireland Research Centre for Pharmaceuticals, Ireland

^c Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland

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.

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DOI: https://doi.org/10.1039/D3CC03340F
Article type: Communication
Submitted: 11 Jul 2023
Accepted: 28 Sep 2023
First published: 28 Sep 2023
This article is Open Access

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Chem. Commun., 2023,59, 12641-12644

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

P. D. O’Dowd, G. P. Sullivan, D. A. Rodrigues, T. N. Chonghaile and D. M. Griffith, Chem. Commun., 2023, 59, 12641 DOI: 10.1039/D3CC03340F

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Chemical Communications

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

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

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