Raghavendra Nulgumnalli Manjunathaiah, Pingili Divya, Kadasi Sundeep, Mettu Akhila, Prasad S V U M
Center for Technological Development in Health, National Institute of Science and Technology on Innovation on Neglected Diseases, Fiocruz, Rio de Janeiro, Brazil.
Sri Venkateshwara College of Pharmacy, Osmania University, Hyderabad, India; Department of Pharmacy, Jawaharlal Nehru Technological University, Kakinada, India.
Eur J Med Chem. 2018 Jan 1;143:1277-1300. doi: 10.1016/j.ejmech.2017.10.021. Epub 2017 Oct 10.
Dual-targeting/Multi-targeting of oncoproteins by a single drug molecule represents an efficient, logical and alternative approach to drug combinations. An increasing interest in this approach is indicated by a steady upsurge in the number of articles on targeting dual/multi proteins published in the last 5 years. Combining different inhibitors that destiny specific single target is the standard treatment for cancer. A new generation of dual or multi-targeting drugs is emerging, where a single chemical entity can act on multiple molecular targets. Dual/Multi-targeting agents are beneficial for solving limited efficiencies, poor safety and resistant profiles of an individual target. Designing dual/multi-target inhibitors with predefined biological profiles present a challenge. The latest advances in bioinformatic tools and the availability of detailed structural information of target proteins have shown a way of discovering multi-targeting molecules. This neoteric artifice that amalgamates the molecular docking of small molecules with protein-based common pharmacophore to design multi-targeting inhibitors is gaining great importance in anticancer drug discovery. Current review focus on the discoveries of dual targeting agents in cancer therapy using rational, computational, proteomic, bioinformatics and polypharmacological approach that enables the discovery and rational design of effective and safe multi-target anticancer agents.
通过单一药物分子对癌蛋白进行双靶点/多靶点作用代表了一种有效、合理且可替代联合用药的方法。过去5年中，关于靶向双蛋白/多蛋白的文章数量稳步上升，这表明人们对该方法的兴趣与日俱增。联合针对特定单一靶点的不同抑制剂是癌症的标准治疗方法。新一代的双靶点或多靶点药物正在涌现，其中单一化学实体可作用于多个分子靶点。双靶点/多靶点药物有助于解决针对单个靶点时效率有限、安全性差和耐药性等问题。设计具有预定义生物学特性的双靶点/多靶点抑制剂具有挑战性。生物信息学工具的最新进展以及靶蛋白详细结构信息的可得性为发现多靶点分子指明了方向。这种将小分子的分子对接与基于蛋白质的共同药效团相结合以设计多靶点抑制剂的新型技术在抗癌药物研发中变得极为重要。当前综述聚焦于使用合理、计算、蛋白质组学、生物信息学和多药理学方法在癌症治疗中发现双靶点药物，这些方法能够实现有效且安全的多靶点抗癌药物的发现与合理设计。
