Monovalent cation ionophore that displays selectivity for K+ and NH4+
CAS：6833-84-7
分子式：C40H64O12
分子量：736.94
纯度：98%
存储：Store at -20°C

Background:

Nonactin, monactin, and dinactin mixture is a macrotetralide antibiotic.[1] This product is a mixture of the macrotetralide antibiotic homologs nonactin, monactin, and dinactin that all act as ionophores for monovalent cations.[2],[3],[4],[5],[6],[7] Nonactin is a mitochondrial membrane uncoupler and an inhibitor of adenine nucleotide translocase (ANT; IC50s = 4.4, 3.3, 4.7, and 3.3 μM for recombinant human ANT1-4, respectively).[8],[9] It selectively induces apoptosis in cancer cells and induces tumor regression in mouse xenograft models expressing mutant β-catenin over cancer cells and xenografts expressing wild-type β-catenin.8 Monactin induces swelling of rat liver mitochondria in medium containing either potassium or sodium, stimulates respiration, and uncouples oxidative phosphorylation.[10] It also inhibits Wnt signaling via inhibition of TCF-β-catenin transcriptional activity.[11] Dinactin inhibits T cell proliferation and cytokine production in vitro and reduces pulmonary eosinophilia in antigen-challenged mice.[12]Reference:
[1]. Pampaloni, F., Mayer, B., Kabat Vel-Job, K., et al. A novel cellular spheroid-based autophagy screen applying live fluorescence microscopy identifies nonactin as a strong inducer of autophagosomal turnover. SLAS Discov. 22(5), 558-570 (2017).
[2]. Hall, J.E., and Latorre, R. Nonactin-K+ complex as a probe for membrane asymmetry. Biophys.J. 16(1), 99-103 (1976).
[3]. Browne, A., and O'Donnell, M.J. Ammonium secretion by Malpighian tubules of Drosophila melanogaster: Application of a novel ammonium-selective microelectrode. J.Exp.Biol. 216(Pt 20), 3818-3827 (2013).
[4]. Skulskii, I.A., Saris, N.-E.L., Savina, M.V., et al. Uptake of thallous ions by mitochondria is stimulated by nonactin but not by respiration alone. Eur.J.Biochem. 120(2), 263-266 (1981).
[5]. Beck, J., Gerlach, H., Prelog, V., et al. Metabolic products of actinomycetes. XXXV. Constitution of the macrotetrolides, monactin, dinactin, and trinactin. Helvetica Chimica Acta 45, 620-630 (1962).
[6]. Harold, F.M., and Baarda, J.R. Effects of nigericin and monactin on cation permeability of Streptococcus faecalis and metabolic capacities of potassium-depleted cells. J. Bacteriol. 95(3), 816-823 (1968).
[7]. Laprade, R., Grenier, F., Pagé-Dansereau, M., et al. Carrier-mediated ion transport in lipid bilayer membranes. Can. J. Biochem. Cell Biol. 62(8), 738-751 (1984).
[8]. Shikata, Y., Kiga, M., Futamura, Y., et al. Mitochondrial uncoupler exerts a synthetic lethal effect against β-catenin mutant tumor cells. Cancer Sci. 108(4), 772-784 (2017).
[9]. Zhang, Y., Tian, D., Matsuyama, H., et al. Human adenine nucleotide translocase (ANT) modulators identified by high-throughput screening of transgenic yeast. J. Biomol. Screen. 21(4), 381-390 (2016).
[10]. Graven, S.N., Lardy, H.A., and Estrada-O, S. Antibiotics as tools for metabolic studies. 8. Effect of nonactin homologs on alkali metal cation transport and rate of respiration in mitochondria. Biochem. 6(2), 365-371 (1967).
[11]. Tamai, Y., Toume, K., Arai, M.A., et al. Nonactin and related compounds found in a screening program for Wnt signal inhibitory activity. Heterocycles 84(2), 1245-1250 (2012).
[12]. Umland, S.P., Shah, H., Jakway, J.P., et al. Effects of cyclosporin A and dinactin on T-cell proliferation, interleukin-5 production, and murine pulmonary inflammation. Am. J. Respir. Cell Mol. Biol. 20(3), 481-492 (1999).