biostudies-literature00470Borsari CAssociazione Italiana per la Ricerca sul Cancro1908-1928https://www.ebi.ac.uk/biostudies/studies/S-EPMC7997565biostudies-literatureUnknown63(5)After the first seed concept introduced in the 18th century, different disciplines have attributed different names to dual-functional molecules depending on their application, including bioconjugates, bifunctional compounds, multitargeting molecules, chimeras, hybrids, engineered compounds. However, these engineered constructs share a general structure: a first component that targets a specific cell and a second component that exerts the pharmacological activity. A stable or cleavable linker connects the two modules of a chimera. Herein, we discuss the recent advances in the rapidly expanding field of chimeric molecules leveraging chemical biology concepts. This Perspective is focused on bifunctional compounds in which one component is a lead compound or a drug. In detail, we discuss chemical features of chimeric molecules and their use for targeted delivery and for target engagement studies.Journal of medicinal chemistryDesigning Chimeric Molecules for Drug Discovery by Leveraging Chemical Biology.PMC7997565AIRC IG16977Costi MPTait ATrader DJBorsari C47falseDesigning Chimeric Molecules for Drug Discovery by Leveraging Chemical Biology.After the first seed concept introduced in the 18th century, different disciplines have attributed different names to dual-functional molecules depending on their application, including bioconjugates, bifunctional compounds, multitargeting molecules, chimeras, hybrids, engineered compounds. However, these engineered constructs share a general structure: a first component that targets a specific cell and a second component that exerts the pharmacological activity. A stable or cleavable linker connects the two modules of a chimera. Herein, we discuss the recent advances in the rapidly expanding field of chimeric molecules leveraging chemical biology concepts. This Perspective is focused on bifunctional compounds in which one component is a lead compound or a drug. In detail, we discuss chemical features of chimeric molecules and their use for targeted delivery and for target engagement studies.2020-01-01T00:00:00Z2020 Mar2024-11-20T17:50:45.492Z2022-02-09T10:18:04.825ZS-EPMC79975653202305510.1021/acs.jmedchem.9b01456