癌症、代谢综合征或神经退行性疾病等复杂和多因素的人类疾病的核心是多个参与者在强大的生物网络中相互交流，这些生物网络本质上对变化具有弹性。这些多因素疾病的特点是复杂的反馈机制，表现为细胞失衡和对药物治疗的抵抗。通过遵循特异性范式（“一靶一药概念”），多年来研究重点关注作用机制非常狭窄的药物。这种狭隘的焦点导致了治疗的无效性和抵抗力。然而，现代药物发现在过去几年中不断发展，越来越强调开发临床有效药物的整体策略。这些整体策略包括控制多个靶点的参与以克服治疗阻力。除了治疗中的附加甚至协同效应外，多靶点药物还具有分子结构属性，可以探索孤儿靶点，其内在底物/生理作用和/或调节剂对于未来的治疗目的是未知的。我们将药物化学、化学生物学和分子药理学之间的多学科和转化研究领域指定为“药物多药理学”。药物多药理学作为常见单靶点药理学的替代方法出现，从基本药物和靶点识别过程延伸到多靶点药物的临床评价，而“多药组”的探索和开发处于现代药物开发研究的前沿。© 2023作者。药物开发研究由 Wiley periodicals LLC 出版。

At the core of complex and multifactorial human diseases, such as cancer, metabolic syndrome, or neurodegeneration, are multiple players that cross-talk in robust biological networks which are intrinsically resilient to alterations. These multifactorial diseases are characterized by sophisticated feedback mechanisms which manifest cellular imbalance and resistance to drug therapy. By adhering to the specificity paradigm ("one target-one drug concept"), research focused for many years on drugs with very narrow mechanisms of action. This narrow focus promoted therapy ineffectiveness and resistance. However, modern drug discovery has evolved over the last years, increasingly emphasizing integral strategies for the development of clinically effective drugs. These integral strategies include the controlled engagement of multiple targets to overcome therapy resistance. Apart from the additive or even synergistic effects in therapy, multitarget drugs harbor molecular-structural attributes to explore orphan targets of which intrinsic substrates/physiological role(s) and/or modulators are unknown for future therapy purposes. We designated this multidisciplinary and translational research field between medicinal chemistry, chemical biology, and molecular pharmacology as 'medicinal polypharmacology'. Medicinal polypharmacology emerged as alternative approach to common single-targeted pharmacology stretching from basic drug and target identification processes to clinical evaluation of multitarget drugs, and the exploration and exploitation of the 'polypharmacolome' is at the forefront of modern drug development research.© 2023 The Authors. Drug Development Research published by Wiley Periodicals LLC.