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 transfer

copper 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].

Reference:
[1].  Wang J, Luo C, Shan CL, et al. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation. Nature Chemistry, 2015, published online 09 November 2015.