Issue 8, 2024

Toward once-monthly insulin therapy via synergy in two pharmacokinetic protractors: Fc-conjugation and fatty acid acylation

Abstract

Pharmacokinetic properties and duration of therapeutic action of a pharmaceutical agent can be significantly extended through the combination of two distinct strategies aimed at increasing plasma half-life: fatty acid acylation and Fc-conjugation. Using insulin as a case study, we demonstrate that a doubly protracted insulin analog produces a substantial prolongation of pharmacodynamic effect to lower blood glucose in STZ-treated mice when compared to the Fc-only counterparts. This enhancement is further corroborated by direct pharmacokinetic measurements in rat and dog models, demonstrating the potential for once-monthly insulin therapy. The results suggest that this approach might have broad application across a diverse spectrum of peptide- and protein-based therapeutics.

Graphical abstract: Toward once-monthly insulin therapy via synergy in two pharmacokinetic protractors: Fc-conjugation and fatty acid acylation

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Article information

Article type
Paper
Submitted
06 Apr 2024
Accepted
17 Jun 2024
First published
18 Jun 2024
This article is Open Access
Creative Commons BY license

RSC Chem. Biol., 2024,5, 763-775

Toward once-monthly insulin therapy via synergy in two pharmacokinetic protractors: Fc-conjugation and fatty acid acylation

A. N. Zaykov, V. M. Gelfanov, T. M. Tagmose, D. Demozay, V. Manfè, R. Rohlfs, M. Rivir, D. Perez-Tilve, B. Finan and R. D. DiMarchi, RSC Chem. Biol., 2024, 5, 763 DOI: 10.1039/D4CB00078A

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