ArticleNature chemistry2019
Rapamycin-inspired macrocycles with new target specificity.
Article in Nature chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 122 citations in OpenAlex.
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- High-throughput ligand discovery in living cells using the cellular protein stability enhancement assay.Acta pharmaceutica Sinica. B · 2026Article
- Discovery of molecular glues that bind FKBP12 and structurally distinct targets using DNA-encoded libraries.Nature communications · 2026Article
- Induced proximity-based therapeutic modalities.Nature reviews. Drug discovery · 2026Review
- Macrocyclic Molecular Glues for the 14-3-3/ChREBP Interaction: Affinity and Cooperativity in an Inverse Relationship.Angewandte Chemie (International ed. in English) · 2026Article
- A MAM-targeting therapeutic peptide restores autophagy homeostasis and ameliorates atherosclerosis.Theranostics · 2026Article
- Identification and characterization of binders to a cryptic and functional pocket in KRAS.Nature communications · 2025Article
- A Convergent Approach to Resorcinolic Macrolides to Expand Structural Diversity.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- A Sydnonimine-based Click-and-Release Approach to Cyclic Products.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Nondegradative Synthetic Molecular Glues Enter the Clinic.ChemMedChem · 2025Review
- Identification of Rapaglutin E as an Isoform-Specific Inhibitor of Glucose Transporter 1.ACS chemical biology · 2025Article
- Rapavir, a novel inhibitor of sodium taurocholate cotransporting polypeptide, potently blocks hepatitis B virus entry.Signal transduction and targeted therapy · 2025Article
- Research advancements in molecular glues derived from natural product scaffolds: Chemistry, targets, and molecular mechanisms.Chinese herbal medicines · 2025Review
- Development of an FKBP12-recruiting chemical-induced proximity DNA-encoded library and its application to discover an autophagy potentiator.Cell chemical biology · 2025Article
- Parthanatos: Mechanisms, modulation, and therapeutic prospects in neurodegenerative disease and stroke.Biochemical pharmacology · 2024Review
- Irisin-Encapsulated Mitochondria-Targeted Biomimetic Nanotherapeutics for Alleviating Acute Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 5 countries.
Funding
Abstract
Rapamycin and FK506 are macrocyclic natural products with an extraordinary mode of action, in which they form binary complexes with FK506-binding protein (FKBP) through a shared FKBP-binding domain before forming ternary complexes with their respective targets, mechanistic target of rapamycin (mTOR) and calcineurin, respectively. Inspired by this, we sought to build a rapamycin-like macromolecule library to target new cellular proteins by replacing the effector domain of rapamycin with a combinatorial library of oligopeptides. We developed a robust macrocyclization method using ring-closing metathesis and synthesized a 45,000-compound library of hybrid macrocycles (named rapafucins) using optimized FKBP-binding domains. Screening of the rapafucin library in human cells led to the discovery of rapadocin, an inhibitor of nucleoside uptake. Rapadocin is a potent, isoform-specific and FKBP-dependent inhibitor of the equilibrative nucleoside transporter 1 and is efficacious in an animal model of kidney ischaemia reperfusion injury. Together, these results demonstrate that rapafucins are a new class of chemical probes and drug leads that can expand the repertoire of protein targets well beyond mTOR and calcineurin.
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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.