Endosidin 5

Endosidin5 (ES5) is an inhibitor of endosomal recycling and dCTP pyrophosphatase 1 (dCTPase 1; IC₅₀ = 1 µM for the human enzyme).^1,2 It induces trafficking of endocytosed plasma membrane to the vacuole in Arabidopsis cells and inhibits the recycling of plasma membrane proteins in HeLa cells.¹ ES5 inhibits membrane remodeling mediated by annexin A6 in HEK293T cell lysates (EC₅₀ = ~3 µM) and enhances the delivery of mRNA via lipid nanoparticles (LNPs) in HEK293T cells in an annexin A6-dependent manner.³

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1. Drakakaki, G., Robert, S., Szatmari, A.-M., et al. Clusters of bioactive compounds target dynamic endomembrane networks in vivo. Proc. Natl. Acad. Sci. USA 108(43), 17850-17855 (2011).

2. Llona-Minguez, S., Häggblad, M., Martens, U., et al. Diverse heterocyclic scaffolds as dCTP pyrophosphatase 1 inhibitors. Part 1: Triazoles, triazolopyrimidines, triazinoindoles, quinoline hydrazones and arylpiperazines. Bioorg. Med. Chem. Lett. 27(16), 3897-3904 (2017).

3. Shin, J., Douglas, C.J., Zhang, S., et al. Targeting recycling endosomes to potentiate mRNA lipid nanoparticles. Nano Lett. 24(17), 5104-5109 (2024).