BE-43547 is a bacteria-derived, which targets hypoxic cells independently of reductases. It was isolated as a mixture of congeners (A1-C2) from Micromonospora sp. The macrocyclic depsipeptide BE-43547, produced by some bacteria in hypoxic niches, possibly to kill competing microorganisms, shows selective cytotoxicity against hypoxic cells. The compound was recently shown to covalently target eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) under oxic conditions. Under hypoxia, BE-43547 induces necrotic cell death involving rapid loss of mitochondrial function and integrity with phenotypic similarities to ferroptosis, yet lacking the critical markers of this type of cell death. The hypoxia-selective toxicity of BE-43547 is shared with the structurally related rakicidin-family of natural products; however, BE-43547 displayed enhanced hypoxia selectivity when tested in pancreatic PANC-1 cells. Furthermore, the full potential of this drug remains uncertain, including benchmarking against a lead bioreductive agent[1].
