Departments of Oncology, Pharmacology and Pathology, and Developmental Therapeutics Program, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, 4100 John R Street Hudson Webber Cancer Research Center Room 516, Detroit, MI 48201, USA.
Mini Rev Med Chem. 2012 Oct;12(12):1193-201. doi: 10.2174/138955712802762040.
Dithiocarbamates are a class of metal-chelating compounds with various applications in medicine. They have been used for the treatment of bacterial and fungal infections, possible treatment of AIDS, and most recently cancer. Their anti-tumor effects can in part be attributed to their ability to complex tumor cellular copper, leading to binding to and inhibition of the proteasome and in turn initiating tumor cell-specific apoptosis. Current chemotherapeutic agents are highly toxic and therefore their efficacy in the eradication of tumors is greatly limited. As a result many scientists have joined the quest for novel targeted therapies in hopes of reducing toxicity while maximizing potency and proteasome inhibition has become an attractive therapy in this regard. Here we discuss the origins, mechanism, and evolution of dithiocarbamates as potent proteasome inhibitors and therefore anti-cancer agents.
二硫代氨基甲酸盐是一类金属螯合剂化合物，在医学中有多种应用。它们已被用于治疗细菌和真菌感染，可能用于治疗艾滋病，最近还用于治疗癌症。它们的抗肿瘤作用部分归因于它们能够与肿瘤细胞内的铜结合，从而与蛋白酶体结合并抑制其活性，进而引发肿瘤细胞特异性凋亡。目前的化疗药物毒性很高，因此它们在消灭肿瘤方面的疗效受到极大限制。因此，许多科学家加入了寻找新型靶向治疗的行列，希望在降低毒性的同时最大限度地提高效力，而蛋白酶体抑制已成为这方面的一种有吸引力的治疗方法。在这里，我们讨论二硫代氨基甲酸盐作为有效的蛋白酶体抑制剂，因此作为抗癌剂的起源、机制和演变。
