Issue 7, 2020

A successful search for new, efficient, and silver-free manufacturing processes for key platinum(ii) intermediates applied in antibody–drug conjugate (ADC) production

Abstract

A silver-free amination procedure, here called “complexation”, was developed to obtain a class of Pt(II) complexes bearing a payload (such as a diagnostic or a therapeutic moiety). These complexes are crucial intermediates for the efficient development and production of antibody–drug conjugates (ADCs) based on a novel Pt(II)-based linker technology. We termed this metal–organic linker, [ethylenediamineplatinum(II)]2+, “Lx”®. The present, newly developed procedure is a greener alternative for the classically applied activation reaction of Pt-halido complexes with silver salts, followed by amination. The crucial finding is that the leaving ligand of the classical process, chloride, can now be replaced by its higher homologue iodide. This not only decisively improved the manufacturing process of the intermediate, but also was found to be key to a more efficient conjugation procedure, i.e. a subsequent step in which this intermediate is coupled to an antibody. The new process allowed upscaling to be readily realized and the desired intermediate was successfully manufactured on a multigram scale. The obtained Ag-free procedure can be generalized and has a great potential to be applied for other Pt(II) complexes of high importance, such as anti-cancer therapeutics.

Graphical abstract: A successful search for new, efficient, and silver-free manufacturing processes for key platinum(ii) intermediates applied in antibody–drug conjugate (ADC) production

Supplementary files

Article information

Article type
Paper
Submitted
05 Sep 2019
Accepted
20 Dec 2019
First published
05 Feb 2020
This article is Open Access
Creative Commons BY-NC license

Green Chem., 2020,22, 2203-2212

A successful search for new, efficient, and silver-free manufacturing processes for key platinum(II) intermediates applied in antibody–drug conjugate (ADC) production

E. Merkul, N. J. Sijbrandi, I. Aydin, J. A. Muns, R. J. R. W. Peters, P. Laarhoven, H. Houthoff and G. A. M. S. van Dongen, Green Chem., 2020, 22, 2203 DOI: 10.1039/C9GC03130H

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements