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Overview
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Background
DC_AC50 is a selective inhibitor of human copper-trafficking proteins Atox1 and CCS with Kd values of ∼6.8 μM and ∼8.2 μM [1]. Human copper-trafficking proteins Atox1 and CCS are cytosolic copper chaperones that transfercopper to specific cellular destinations [1]. DC_AC50 is a selective inhibitor of human copper-trafficking proteins Atox1 and CCS. DC_AC50 is a self-fluorescing compound with excitations at 290 nm and 355 nm, and emission at 494 nm. In FRET assay, DC_AC50 bound to Atox1 and full-length CCS with Kd values of ∼6.8 μM and 8.2 μM. In fluorescence anisotropy (FA) assay, DC_AC50 bound to Atox1, full-length CCS and CCS domain I with Kd values of 6.4 μM, 7.9 μM and 12.2 μM. In human lung cancer H1299 cells, leukaemia cancer K562 cells, breast cancer MDA-MB-231 cells and head and neck cancer 212LN cells, DC_AC50 dose-dependently inhibited cancer cell proliferation by targeting Atox1 and CCS. DC_AC50 also induced reactive oxygen species (ROS) accumulation, reduced cellular ATP production and decreases lipid biosynthesis via AMP-activated protein kinase (AMPK) activation [1]. In nude mice bearing lung cancer H1299 cells or leukaemia cancer K562 cells, DC_AC50 (100 mg/kg per day for 21 days) significantly decreased tumour size compared with vehicle control. In K562 mice model, DC_AC50 (10, 20 and 50 mg/kg per day) also induced a similar tumor-inhibition effects without any obvious toxicity or a change in body weight [1].
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- Properties
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Overview