ArticleProceedings of the National Academy of Sciences of the United States of America2008
Overcoming multidrug resistance of small-molecule therapeutics through conjugation with releasable octaarginine transporters.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 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
99 citing papers in PubMed, 250 citations in OpenAlex.
- Multi-omic integration identifies broad drug resistance mechanisms and strategies to therapeutically reprogram cancer cells.iScience · 2026Article
- In Vivo Interrogation of Cell-Penetrating Peptide Function: Accumulation in Tumors and the Potential as a Specific PET Probe.Bioconjugate chemistry · 2025Article
- Biological Properties of Arginine-rich Peptides and their Application in Cargo Delivery to Cancer.Current drug delivery · 2025Review
- Biguanide-Vancomycin Conjugates are Effective Broad-Spectrum Antibiotics against Actively Growing and Biofilm-Associated Gram-Positive and Gram-Negative ESKAPE Pathogens and Mycobacteria.Journal of the American Chemical Society · 2024Article
- One chiral fingerprint to find them all.Journal of cheminformatics · 2024Article
- Smart Delivery Systems Responsive to Cathepsin B Activity for Cancer Treatment.Pharmaceutics · 2023Review
- Detection of intact vancomycin-arginine as the active antibacterial conjugate inRSC medicinal chemistry · 2023Article
- Dimeric Metal-Salphen Complexes Which Target Multimeric G-Quadruplex DNA.Bioconjugate chemistry · 2023Article
- Poly(l-Ornithine)-Based Polymeric Micelles as pH-Responsive Macromolecular Anticancer Agents.Pharmaceutics · 2023Article
- Targeting Carbohydrate Mimetics of Tetrahydrofuran-Containing Acetogenins to Prostate Cancer.Molecules (Basel, Switzerland) · 2023Article
- Stimuli-Responsive Boron-Based Materials in Drug Delivery.International journal of molecular sciences · 2023Review
- Recent Advances in Natural Product-Based Hybrids as Anti-Cancer Agents.Molecules (Basel, Switzerland) · 2022Review
- Collagen-Binding Peptide-Enabled Supramolecular Hydrogel Design for Improved Organ Adhesion and Sprayable Therapeutic Delivery.Nano letters · 2022Article
- Divalent Metal Ions Boost Effect of Nucleic Acids Delivered by Cell-Penetrating Peptides.Cells · 2022Article
- Cell-penetrating peptides improve pharmacokinetics and pharmacodynamics of anticancer drugs.Tissue barriers · 2022Review
- A Concise Review on the Role of Natural and Synthetically Derived Peptides in Colorectal Cancer.Current topics in medicinal chemistry · 2022Review
- Cell-Penetrating Peptides: Applications in Tumor Diagnosis and Therapeutics.Pharmaceutics · 2021Review
- Development of an Acid-Labile Ketal Linked Amphiphilic Block Copolymer Nanoparticles for pH-Triggered Release of Paclitaxel.Polymers · 2021Article
- The Interaction of Supramolecular Anticancer Drug Amphiphiles with Phospholipid Membranes.Nanoscale advances · 2021Article
- SPA: a peptide antagonist that acts as a cell-penetrating peptide for drug delivery.Drug delivery · 2020Article
39 more citing papers are in PubMed but not listed here.
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 at 1 institution in 1 country.
Funding
Abstract
Many cancer therapeutic agents elicit resistance that renders them ineffective and often produces cross-resistance to other drugs. One of the most common mechanisms of resistance involves P-glycoprotein (Pgp)-mediated drug efflux. To address this problem, new agents have been sought that are less prone to inducing resistance and less likely to serve as substrates for Pgp efflux. An alternative to this approach is to deliver established agents as molecular transporter conjugates into cells through a mechanism that circumvents Pgp-mediated efflux and allows for release of free drug only after cell entry. Here we report that the widely used chemotherapeutic agent Taxol, ineffective against Taxol-resistant human ovarian cancer cell lines, can be incorporated into a releasable octaarginine conjugate that is effective against the same Taxol-resistant cell lines. It is significant that the ability of the Taxol conjugates to overcome Taxol resistance is observed both in cell culture and in animal models of ovarian cancer. The generality and mechanistic basis for this effect were also explored with coelenterazine, a Pgp substrate. Although coelenterazine itself does not enter cells because of Pgp efflux, its octaarginine conjugate does so readily. This approach shows generality for overcoming the multidrug resistance elicited by small-molecule cancer chemotherapeutics and could improve the prognosis for many patients with cancer and fundamentally alter search strategies for novel therapeutic agents that are effective against resistant disease.
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.