Pharmacological Reports ( IF 3.6 ) Pub Date : 2023-06-06 , DOI: 10.1007/s43440-023-00501-4
Piotr Ryszkiewicz 1 , Barbara Malinowska 1 , Eberhard Schlicker 2
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Polypharmacology is an emerging strategy of design, synthesis, and clinical implementation of pharmaceutical agents that act on multiple targets simultaneously. It should not be mixed up with polytherapy, which is based on the use of multiple selective drugs and is considered a cornerstone of current clinical practice. However, this ‘classic’ approach, when facing urgent medical challenges, such as multifactorial diseases, increasing resistance to pharmacotherapy, and multimorbidity, seems to be insufficient. The ‘novel’ polypharmacology concept leads to a more predictable pharmacokinetic profile of multi-target-directed ligands (MTDLs), giving a chance to avoid drug-drug interactions and improve patient compliance due to the simplification of dosing regimens. Plenty of recently marketed drugs interact with multiple biological targets or disease pathways. Many offer a significant additional benefit compared to the standard treatment regimens. In this paper, we will briefly outline the genesis of polypharmacology and its differences to polytherapy. We will also present leading concepts for obtaining MTDLs. Subsequently, we will describe some successfully marketed drugs, the mechanisms of action of which are based on the interaction with multiple targets. To get an idea, of whether MTDLs are indeed important in contemporary pharmacology, we also carefully analyzed drugs approved in 2022 in Germany: 10 out of them were found multi-targeting, including 7 antitumor agents, 1 antidepressant, 1 hypnotic, and 1 drug indicated for eye disease.
中文翻译:
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多药理学:2022 年的前景和新药
多药理学是一种同时作用于多个靶点的药剂的设计、合成和临床实施的新兴策略。它不应与多重疗法相混淆,多重疗法基于使用多种选择性药物,被认为是当前临床实践的基石。然而,当面临多因素疾病、药物治疗耐药性增加和多重发病等紧迫的医学挑战时,这种“经典”方法似乎还不够。“新颖”的多药理学概念使多靶点定向配体(MTDL)的药代动力学特征更加可预测,从而有机会避免药物间相互作用,并由于给药方案的简化而提高患者的依从性。最近上市的许多药物与多个生物靶点或疾病途径相互作用。与标准治疗方案相比,许多治疗方案具有显着的额外益处。在本文中,我们将简要概述多重药理学的起源及其与多重疗法的差异。我们还将介绍获取 MTDL 的领先概念。随后,我们将描述一些成功上市的药物,其作用机制基于与多个靶点的相互作用。为了了解 MTDL 在当代药理学中是否确实重要,我们还仔细分析了 2022 年在德国批准的药物:其中 10 种被发现具有多靶点,包括 7 种抗肿瘤药、1 种抗抑郁药、1 种安眠药和 1 种药物适用于眼部疾病。