National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswaldo Cruz, Ministério da Saúde, Av. Brazil 4036, Prédio da Expansão, 8° Andar, Sala 814, Manguinhos , 21040-361 Rio de Janeiro , RJ , Brazil.
Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Institute of Biomedical Sciences , Federal University of Rio de Janeiro (UFRJ) , P.O. Box 68023, 21941-902 Rio de Janeiro , RJ , Brazil.
J Med Chem. 2018 Jul 26;61(14):5805-5821. doi: 10.1021/acs.jmedchem.7b01689. Epub 2018 Feb 26.
Metal based therapeutics are a precious class of drugs in oncology research that include examples of theranostic drugs, which are active in both diagnostic, specifically imaging, and therapeutics applications. Ruthenium compounds have shown selective bioactivity and the ability to overcome the resistance that platinum-based therapeutics face, making them effective oncotherapeutic competitors in rational drug invention approaches. The development of antineoplastic ruthenium therapeutics is of particular interest because ruthenium containing complexes NAMI-A, KP1019, and KP1339 entered clinical trials and DW1/2 is in preclinical levels. The very robust, conformationally rigid organometallic Ru(II) compound DW1/2 is a protein kinase inhibitor and presents new Ru(II) compound designs as anticancer agents. Over the recent years, numerous strategies have been used to encapsulate Ru(II) derived compounds in a nanomaterial system, improving their targeting and delivery into neoplastic cells. A new photodynamic therapy based Ru(II) therapeutic, TLD-1433, has also entered clinical trials. Ru(II)-based compounds can also be photosensitizers for photodynamic therapy, which has proven to be an effective new, alternative, and noninvasive oncotherapy modality.
金属基治疗药物是肿瘤学研究中一类珍贵的药物，其中包括治疗诊断药物的例子，这些药物在诊断，特别是成像和治疗应用中都具有活性。钌化合物表现出选择性生物活性，并能够克服铂类治疗药物所面临的耐药性，使它们成为合理药物发明方法中有效的肿瘤治疗竞争者。开发抗肿瘤钌治疗药物特别有趣，因为含钌的配合物 NAMI-A、KP1019 和 KP1339 已经进入临床试验，DW1/2 处于临床前阶段。非常坚固、构象刚性的有机金属 Ru(II)化合物 DW1/2 是一种蛋白激酶抑制剂，并提出了新的 Ru(II)化合物设计作为抗癌剂。近年来，人们已经使用了多种策略将 Ru(II)衍生化合物封装在纳米材料系统中，以提高它们对肿瘤细胞的靶向性和递送能力。一种新的基于光动力治疗的 Ru(II)治疗药物 TLD-1433 也已经进入临床试验。Ru(II)基化合物也可以作为光动力治疗的光敏剂，光动力治疗已被证明是一种有效的新的、替代的、非侵入性的肿瘤治疗方法。
