DC_AC50 is a small molecule that inhibits the copper-trafficking proteins ATOX-1 and CCS, with Kd values of 6.8±1.7µM and 8.2±2.7µM, respectively[1]. DC_AC50 is a self-fluorescing compound with excitations at 290nm and 355nm, and emission at 494nm[1]. DC_AC50 can block the copper transport interface of the two major copper chaperones ATOX-1 and CCS to increase intracellular copper levels and lead to enhanced oxidative stress in the cells[2]. DC_AC50 has been widely used to enhance intracellular reactive oxygen species (ROS) levels and inhibit tumor cell growth[3].
In vitro, DC_AC50 treatment for 72 hours significantly inhibited the viability of Abrams and D17 cells with IC50 values of 9.88µM and 12.57µM, respectively[4]. Treatment with 25μM DC_AC50 for 7 days can effectively inhibit the proliferation of BRAF-mutated melanoma cells and weaken the activation of the MAPK pathway[5]. Treatment with 10μM DC_AC50 for 24 hours significantly inhibited the growth of HepG2 cells, while promoting the accumulation of ROS and cell apoptosis[6]. 20µM of DC_AC50 pretreatment for 24 hours significantly inhibited the production of ROS and the M1 polarization of mouse macrophages induced by CuCl2[7].
In vivo, DC_AC50 treatment via intraperitoneal injection at a dose of 50mg/kg/day for 5 weeks inhibited tumor growth and suppressed angiogenesis in mice of MDA-MB-468 xenograft model[8]. Intraperitoneal injection of 20mg/kg/day dose of DC_AC50 for 21 consecutive days markedly reduced tumor growth in the xenograft mouse model of A549 cells, and suppressed the expression of ATOX1 in the tumors[9].
References:
[1] Wang J, Luo C, Shan C, et al. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation[J]. Nature chemistry, 2015, 7(12): 968-979.
[2] Karginova O, Weekley C, Raoul A, et al. Selective inhibition of copper metabolism as a novel approach to treat triple-negative breast cancer[J]. Cancer Research, 2017, 77(13_Supplement): 3552-3552.
[3] Li W Y, Kan J L, Wan J J, et al. A reactive oxygen species-responsive covalent organic framework for tumor combination therapy[J]. Chemical Communications, 2023, 59(36): 5423-5426.
[4] Inkol J M, Poon A C, Mutsaers A J. Inhibition of copper chaperones sensitizes human and canine osteosarcoma cells to carboplatin chemotherapy[J]. Veterinary and comparative oncology, 2020, 18(4): 559-569.
[5] Kim Y J, Bond G J, Tsang T, et al. Copper chaperone ATOX1 is required for MAPK signaling and growth in BRAF mutation-positive melanoma[J]. Metallomics, 2019, 11(8): 1430-1440.
[6] Ouyang Q, Jia S, Zhu Q, et al. ATOX1 Promotes Hepatocellular Carcinoma Carcinogenesis via Activation of the c-Myb/PI3K/AKT Signaling Pathway[J]. Journal of Clinical and Translational Hepatology, 2025, 13(8): 630.
[7] Chen M X, Chen Y, Fu R, et al. Atox1 regulates macrophage polarization in intestinal inflammation via ROS-NLRP3 inflammasome pathway[J]. Journal of Translational Medicine, 2024, 22(1): 497.
[8] Karginova O, Weekley C M, Raoul A, et al. Inhibition of copper transport induces apoptosis in triple-negative breast cancer cells and suppresses tumor angiogenesis[J]. Molecular cancer therapeutics, 2019, 18(5): 873-885.
[9] Qin X, Wang P, Liang H, et al. Curcumin suppresses copper accumulation in non-small cell lung cancer by binding ATOX1[J]. BMC Pharmacology and Toxicology, 2024, 25(1): 54.
DC_AC50是一种小分子化合物，可抑制铜转运蛋白ATOX-1与CCS，Kd值分别为6.8±1.7µM和8.2±2.7µM[1]。DC_AC50具有自发荧光特性，激发波长为290nm和355nm，发射波长为494nm[1]。DC_AC50通过阻断ATOX-1和CCS的铜转运界面，提高细胞内铜水平并增强氧化应激[2]。DC_AC50已广泛应用于提升细胞内活性氧水平及抑制肿瘤细胞生长[3]。
在体外，DC_AC50处理72小时能显著抑制Abrams和D17细胞活力，IC50值分别为9.88µM和12.57µM[4]。使用25µM的DC_AC50处理BRAF突变型黑色素瘤细胞7天，可有效抑制细胞增殖并减弱MAPK通路活化[5]。用10µM的DC_AC50处理HepG2细胞24小时，能显著抑制细胞生长并促进活性氧积累与细胞凋亡[6]。以20µM的DC_AC50预处理小鼠巨噬细胞24小时，可显著抑制氯化铜诱导的ROS生成及M1型极化[7]。
在体内，每日腹腔注射50mg/kg/day剂量的DC_AC50连续5周，能抑制MDA-MB-468移植瘤小鼠的肿瘤生长与血管发生[8]。连续21天每日腹腔注射20mg/kg/day剂量的DC_AC50，可显著抑制A549细胞异种移植瘤小鼠模型的肿瘤生长，并降低肿瘤组织中ATOX1蛋白表达[9]。