支架跳跃是一种设计方法，涉及改变已有生物活性支架的核心结构，以生成新分子，从而发现具有创新核心结构的生物活性命中化合物。支架跳跃增强了选择性和效力，同时保持了理化、药效 (PD) 和药代动力学 (PK) 特性，包括毒性参数。基于支架跳跃策略设计了许多分子，这些分子对不同类型的恶性肿瘤的多个靶点表现出有效的抑制活性。在这篇综述中，我们批判性地讨论了支架跳跃的最新应用以及药物化学的重要组成部分，例如构效关系（SAR）概况。此外，我们还阐明了基于支架跳跃的抗癌药物发现的局限性和挑战。版权所有 © 2024 Elsevier Ltd。保留所有权利。

Scaffold hopping is a design approach involving alterations to the core structure of an already bioactive scaffold to generate novel molecules to discover bioactive hit compounds with innovative core structures. Scaffold hopping enhances selectivity and potency while maintaining physicochemical, pharmacodynamic (PD), and pharmacokinetic (PK) properties, including toxicity parameters. Numerous molecules have been designed based on a scaffold-hopping strategy that showed potent inhibition activity against multiple targets for the diverse types of malignancy. In this review, we critically discuss recent applications of scaffold hopping along with essential components of medicinal chemistry, such as structure-activity relationship (SAR) profiles. Moreover, we shed light on the limitations and challenges associated with scaffold hopping-based anticancer drug discovery.Copyright © 2024 Elsevier Ltd. All rights reserved.