Emeramide (BDTH2) is a lipid-soluble heavy metal chelator and antioxidant [1]. Emeramide forms strong covalent or semi-covalent thiosulfide complexes with “soft metals” (such as mercury (Hg2+), lead (Pb2+), and cadmium (Cd2+)), thereby reducing the free concentration and toxicity of these metals [2]. Emeramide can help restore or protect intracellular thiol/antioxidant systems, such as glutathione (GSH), thereby alleviating metal-induced oxidative stress [3]. Emeramide is primarily a potential therapeutic agent for heavy metal poisoning [4].
In U-87 MG cells, Emeramide (0-200µM; 24h) reduces cell viability at high concentrations [5]. In HepG2 cells, pretreatment with Emeramide (0-100µM; 24h) reduced CuSO4-induced cell death and decreased ROS levels [6].
In H67D knock-in mutant mice, oral Emeramide (450mg/kg; po; 6 weeks) reduces iron accumulation in the brain and liver [7].
References:
[1]. Secor J D, Kotha S R, Gurney T O, et al. Novel lipid-soluble thiol-redox antioxidant and heavy metal chelator, N, N′-bis (2-mercaptoethyl) isophthalamide (NBMI) and phospholipase D-specific inhibitor, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI) attenuate mercury-induced lipid signaling leading to protection against cytotoxicity in aortic endothelial cells[J]. International journal of toxicology, 2011, 30(6): 619-638.
[2]. Wang Y, Zhang S, Bian J, et al. A method for the rapid detection of heavy metal mercury ions based on a novel mercury chelator N, N'-bis (2-mercaptoethyl) isophthalamide[J]. Food Chemistry, 2025, 468: 142486.
[3]. Secor J D, Kotha S R, Gurney T O, et al. Novel lipid-soluble thiol-redox antioxidant and heavy metal chelator, N, N′-bis (2-mercaptoethyl) isophthalamide (NBMI) and phospholipase D-specific inhibitor, 5-fluoro-2-indolyl des-chlorohalopemide (FIPI) attenuate mercury-induced lipid signaling leading to protection against cytotoxicity in aortic endothelial cells[J]. International journal of toxicology, 2011, 30(6): 619-638.
[4]. Geier D A, Geier M R. Reductions in plasma and urine mercury concentrations following N, N′ bis-(2-mercaptoethyl) isophthalamide (NBMI) therapy: a post hoc analysis of data from a randomized human clinical trial[J]. Biometals, 2024, 37(2): 433-445.
[5]. Gadde R, Betharia S. N, N′ bis-(2-mercaptoethyl) isophthalamide (NBMI) exerts neuroprotection against lead-induced toxicity in U-87 MG cells[J]. Archives of Toxicology, 2021, 95(8): 2643-2657.
[6]. Gadde R, Betharia S. NBMI Exerts Protection Against Copper Overload in HepG2 and SH‐SY5Y Cell Lines[J]. The FASEB Journal, 2022, 36.
[7]. Cheng R, Gadde R, Fan Y, et al. Reversal of genetic brain iron accumulation by N, N′-bis (2-mercaptoethyl) isophthalamide, a lipophilic metal chelator, in mice[J]. Archives of Toxicology, 2022, 96(7): 1951-1962.
Emeramide (BDTH2)是一种脂溶性重金属螯合剂和抗氧化剂 [1]。Emeramide 与“软金属”（例如汞（Hg2+）、铅（Pb2+）和镉（Cd2+））形成强共价或半共价硫代硫化物复合物，从而降低这些金属的游离浓度和毒性 [2]。Emeramide有助于恢复或保护细胞内硫醇/抗氧化系统，例如谷胱甘肽（GSH），从而减轻金属诱导的氧化应激 [3]。Emeramide主要是一种治疗重金属中毒的潜在药物 [4]。
在U-87 MG细胞中，高浓度的Emeramide（0-200µM；24h）可降低细胞活力 [5]。在HepG2细胞中，用Emeramide（0-100µM；24h）预处理可减少CuSO4诱导的细胞死亡并降低活性氧（ROS）水平 [6]。
在H67D敲入突变小鼠中，口服Emeramide（450mg/kg；po；6周）可减少大脑和肝脏中的铁蓄积 [7]。