ArticleChemical science2021
Defining and navigating macrocycle chemical space.
Article in Chemical science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Macrocycle-DB: a comprehensive database for macrocycle-based drug discovery.Nucleic acids research · 2026Article
- Exploring the macrocyclic chemical space for heuristic drug design with deep learning models.Communications chemistry · 2025Article
- Exploring Macrocyclic Chemical Space: Strategies and Technologies for Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A membrane permeability database for nonpeptidic macrocycles.Scientific data · 2025Article
- Exploring chemical space for "druglike" small molecules in the age of AI.Frontiers in molecular biosciences · 2025Review
- The macrocycle inhibitor landscape of SLC-transporter.Molecular informatics · 2024Article
- Targeted sampling of natural product space to identify bioactive natural product-like polyketide macrolides.Nature communications · 2024Article
- Insights on Structure-Passive Permeability Relationship in Pyrrole and Furan-Containing Macrocycles.Journal of medicinal chemistry · 2024Article
- Oral Absorption of Middle-to-Large Molecules and Its Improvement, with a Focus on New Modality Drugs.Pharmaceutics · 2023Review
- Sampling and Mapping Chemical Space with Extended Similarity Indices.Molecules (Basel, Switzerland) · 2023Article
- Macrocyclization of linear molecules by deep learning to facilitate macrocyclic drug candidates discovery.Nature communications · 2023Article
- Lessons for Oral Bioavailability: How Conformationally Flexible Cyclic Peptides Enter and Cross Lipid Membranes.Journal of medicinal chemistry · 2023Article
- Expansion of the genetic code through reassignment of redundant sense codons using fully modified tRNA.Nucleic acids research · 2022Article
- Efficient Crystal Structure Prediction for Structurally Related Molecules with Accurate and Transferable Tailor-Made Force Fields.Journal of chemical theory and computation · 2022Article
- Mapping the binding sites of challenging drug targets.Current opinion in structural biology · 2022Review
- Computational Site Saturation Mutagenesis of Canonical and Non-Canonical Amino Acids to Probe Protein-Peptide Interactions.Frontiers in molecular biosciences · 2022Article
- Improvement on Permeability of Cyclic Peptide/Peptidomimetic: BackboneMarine drugs · 2021Review
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrocyclic compounds (MCs) are of growing interest for inhibition of challenging drug targets. We consider afresh what structural and physicochemical features could be relevant to the bioactivity of this compound class. Using these features, we performed Principal Component Analysis to map oral and non-oral macrocycle drugs and clinical candidates, and also commercially available synthetic MCs, in structure-property space. We find that oral MC drugs occupy defined regions that are distinct from those of the non-oral MC drugs. None of the oral MC regions are effectively sampled by the synthetic MCs. We identify 13 properties that can be used to design synthetic MCs that sample regions overlapping with oral MC drugs. The results advance our understanding of what molecular features are associated with bioactive and orally bioavailable MCs, and illustrate an approach by which synthetic chemists can better evaluate MC designs. We also identify underexplored regions of macrocycle chemical space.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.