ArticleProceedings of the National Academy of Sciences of the United States of America2016
Ultrapotent vinblastines in which added molecular complexity further disrupts the target tubulin dimer-dimer interface.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed.
- Illuminating microtubule functions with small molecules: past, present and future of fluorescent tubulin-binding probes.RSC chemical biology · 2026Review
- PIFA-Mediated Coupling of Vindoline with β-Ketoesters and Related Model Velbanamine Precursors.Synlett : accounts and rapid communications in synthetic organic chemistry · 2026Article
- TargetingPharmaceuticals (Basel, Switzerland) · 2026Article
- Supernatural Products.The Chemist · 2025Article
- Introducing urea into tirapazamine derivatives to enhance anticancer therapy.National science review · 2024Article
- Chemical Reactions of Indole Alkaloids That Enable Rapid Access to New Scaffolds for Discovery.SynOpen (2017) · 2023Article
- Bisindole Alkaloids from theMolecules (Basel, Switzerland) · 2021Review
- Total synthesis of (-)-4-desacetoxy-1-oxovindoline: Single atom exchange of an embedded core heteroatom in vindoline.Tetrahedron · 2021Article
- The quest for supernatural products: the impact of total synthesis in complex natural products medicinal chemistry.Natural product reports · 2020Review
- Perplexing Role of P-Glycoprotein in Tumor Microenvironment.Frontiers in oncology · 2020Review
- Inverse Electron Demand Diels-Alder Reactions of Heterocyclic Azadienes, 1-Aza-1,3-Butadienes, Cyclopropenone Ketals, and Related Systems. A Retrospective.The Journal of organic chemistry · 2019Review
- Ultra-potent vinblastine analogues improve on-target activity of the parent microtubulin-targeting compound.Bioorganic & medicinal chemistry letters · 2019Article
- Inhibit or Evade Multidrug Resistance P-Glycoprotein in Cancer Treatment.Journal of medicinal chemistry · 2018Review
- High expression of class III β-tubulin has no impact on functional cancer cell growth inhibition of a series of key vinblastine analogs.Bioorganic & medicinal chemistry letters · 2018Article
- The Difference a Single Atom Can Make: Synthesis and Design at the Chemistry-Biology Interface.The Journal of organic chemistry · 2017Article
- Vinblastine 20' Amides: Synthetic Analogues That Maintain or Improve Potency and Simultaneously Overcome Pgp-Derived Efflux and Resistance.Journal of medicinal chemistry · 2017Article
- Key analogs of a uniquely potent synthetic vinblastine that contain modifications of the C20' ethyl substituent.Bioorganic & medicinal chemistry letters · 2017Article
- Total synthesis of a key series of vinblastines modified at C4 that define the importance and surprising trends in activity.Chemical science · 2017Article
- Synthesis of Bisindole Alkaloids from the Apocynaceae Which Contain a Macroline or Sarpagine Unit: A Review.Molecules (Basel, Switzerland) · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
Approaches to improving the biological properties of natural products typically strive to modify their structures to identify the essential pharmacophore, or make functional group changes to improve biological target affinity or functional activity, change physical properties, enhance stability, or introduce conformational constraints. Aside from accessible semisynthetic modifications of existing functional groups, rarely does one consider using chemical synthesis to add molecular complexity to the natural product. In part, this may be attributed to the added challenge intrinsic in the synthesis of an even more complex compound. Herein, we report synthetically derived, structurally more complex vinblastines inaccessible from the natural product itself that are a stunning 100-fold more active (IC50 values, 50-75 pM vs. 7 nM; HCT116), and that are now accessible because of advances in the total synthesis of the natural product. The newly discovered ultrapotent vinblastines, which may look highly unusual upon first inspection, bind tubulin with much higher affinity and likely further disrupt the tubulin head-to-tail α/β dimer-dimer interaction by virtue of the strategic placement of an added conformationally well-defined, rigid, and extended C20' urea along the adjacent continuing protein-protein interface. In this case, the added molecular complexity was used to markedly enhance target binding and functional biological activity (100-fold), and likely represents a general approach to improving the properties of other natural products targeting a protein-protein interaction.
Indexed as
Identifiers
What OpenQuestion holds
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.