An in vivo strategy to counteract post-administration anticoagulant activity of azido-Warfarin

Nature Communications
Sylvain UrsueguiAlain Wagner

Abstract

Drugs, usually long acting and metabolically stable molecules, might be the source of adverse effects triggered by complex drug interactions, anaphylaxis and drug-induced coagulopathy. To circumvent this growing drug safety issue, we herein investigate the opportunity offered by bio-orthogonal chemistry for in vivo drug neutralization. We design a small-molecule anticoagulant drug (Warfarin) containing an azide group that acts as a safety pin. It allows drug deactivation and restoration of physiological coagulation via in vivo click reaction with a suitable cyclooctyne-based neutralizing agent. In this strategy, the new molecule formed by reaction of the drug and the antidote is deprived of biological activity and prone to fast renal clearance. This 'Click &Clear' approach lays ground for new strategies in designing drugs with switchable biophysical properties.

References

Feb 1, 1987·The Journal of Pharmacy and Pharmacology·A O Obaseki, H B Coker
Sep 6, 2002·Nature·Christopher P RusconiBruce A Sullenger
Aug 20, 2004·Nature·Jennifer A PrescherCarolyn R Bertozzi
Oct 27, 2004·Nature Biotechnology·Christopher P RusconiBruce A Sullenger
Sep 20, 2006·Angewandte Chemie·Alexander HeckelGünter Mayer
Feb 27, 2007·Journal of the American Chemical Society·Astrid JoachimiJörg S Hartig
May 16, 2009·Drugs·Lily P H Yang, Susan J Keam
Aug 4, 2009·Chembiochem : a European Journal of Chemical Biology·Jing WangGenxi Li
Aug 29, 2009·Angewandte Chemie·Ellen M Sletten, Carolyn R Bertozzi
Oct 6, 2009·Nature Medicine·Sabah OneyBruce A Sullenger
Oct 17, 2009·Journal of Clinical Anesthesia·Anthony L Kovac
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Pamela V ChangCarolyn R Bertozzi
Feb 24, 2010·Chemical Communications : Chem Comm·Reyna K V Lim, Qing Lin
Apr 15, 2010·Angewandte Chemie·Raffaella RossinMarc S Robillard
Mar 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Neal K DevarajRalph Weissleder
Oct 5, 2013·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Raffaella RossinMarc S Robillard
Apr 18, 2014·Bioconjugate Chemistry·Mathias King, Alain Wagner
May 7, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Paul A Burke

❮ Previous
Next ❯

Methods Mentioned

BETA
blood collection

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.

Anaphylaxis

Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death.

Related Papers

La semaine des hôpitaux : organe fondé par l'Association d'enseignement médical des hôpitaux de Paris
M CLOAREC
La Semaine des hôpitaux: thérapeutique
M CLOAREC
The Medical Journal of Australia
D Kwan, W R Bartle
The Journal of the Arkansas Medical Society
Valerie SmithEugene Smith
© 2022 Meta ULC. All rights reserved