Cu (II) -Elesclomol is a 1:1 chelate formed by Elesclomol and Cu (II) ions, which can induce copper death and has anti-cancer activity[1]. Elesclomol is a highly novel anti-cancer drug that has completed Phase 3 clinical trials for patients with advanced melanoma[2]. Both Elesclomol and Cu (II) -elesclomol are highly effective in vitro and usually inhibit the growth of cancer cells at low concentrations[3]. Cu (II) -Elesclomol inhibits the growth of cancer cells by inducing Cu2+ -mediated apoptosis and oxidative stress[1,2].
In vitro, K562 cells were treated with Cu (II) -Elesclomol (0.04, 0.2, 1, 5μM) for 72 hours to induce intracellular H2O2 production, increase intracellular reactive oxygen species levels, and cause oxidative stress in the cells. The IC50 of Cu (II) -Elesclomol on K562 cells was 6.2nM[1,4]. CHO cells were treated with Cu (II) -Elesclomol (50nM) for 30 minutes to induce G1 phase arrest of CHO cells, resulting in rapid cessation of cell growth and induction of cell apoptosis[5].
References:
[1]Hasinoff BB, Yadav AA, Patel D, Wu X. The cytotoxicity of the anticancer drug elesclomol is due to oxidative stress indirectly mediated through its complex with Cu(II). J Inorg Biochem. 2014 Aug;137:22-30.
[2] Nagai M, Vo NH, Shin Ogawa L, Chimmanamada D, Inoue T, Chu J, Beaudette-Zlatanova BC, Lu R, Blackman RK, Barsoum J, Koya K, Wada Y. The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells. Free Radic Biol Med. 2012 May 15;52(10):2142-50.
[3]Hasinoff BB, Yadav AA, Patel D, Wu X. The cytotoxicity of the anticancer drug elesclomol is due to oxidative stress indirectly mediated through its complex with Cu(II). J Inorg Biochem. 2014 Aug;137:22-30.Nov;71(11):1788-1800.
[4]Wu L, Zhou L, Liu DQ, Vogt FG, Kord AS. LC-MS/MS and density functional theory study of copper(II) and nickel(II) chelating complexes of elesclomol (a novel anticancer agent). J Pharm Biomed Anal. 2011 Jan 25;54(2):331-6.
[5]Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, Durez P, Ostor AJ, Li Y, Zhou Y, Othman AA, Genovese MC. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis Rheumatol. 2019 Nov;71(11):1788-1800.
Cu(II)-Elesclomol是Elesclomol与 Cu（II）离子形成的1：1螯合物，能诱导铜死亡，具有抗癌活性[1]。Elesclomol 是一种高度新颖的抗癌药物，已完成针对晚期黑色素瘤患者的3期临床试验[2]。Elesclomol 和 Cu(II)-Elesclomol在体外都非常有效，通常在低浓度下抑制癌细胞生长[3]。Cu(II)-Elesclomol通过诱导通过Cu2+介导的细胞凋亡和氧化应激抑制癌细胞生长[1,2]。
在体外，Cu(II)-Elesclomol（0.04、0.2、1、5μM）处理K562细胞72小时，诱导细胞内H2O2生成，升高细胞内活性氧水平，导致细胞氧化应激。Cu(II)-Elesclomol对K562细胞IC50为6.2nM[1,4]。Cu(II)-Elesclomol（50nM）处理CHO细胞30分钟，诱导CHO细胞G1期阻滞，导致细胞生长迅速停止并诱导细胞凋亡[5]。