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
References:
[1]. Drakakaki, G., Robert, S., Szatmari, A.-M., et al.Clusters of bioactive compounds target dynamic endomembrane networks in vivoProc. Natl. Acad. Sci. USA108(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 arylpiperazinesBioorg. 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 nanoparticlesNano Lett.24(17)5104-5109(2024).