ArticleProceedings of the National Academy of Sciences of the United States of America2014
A new tubulin-binding site and pharmacophore for microtubule-destabilizing anticancer drugs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 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
114 citing papers in PubMed, 276 citations in OpenAlex.
- Eukaryotic-like microtubules and dynamic instability of Asgard archaeal tubulins.Science advances · 2026Article
- PM534, a Novel Colchicine Site Tubulin Inhibitor with Broad-Spectrum and Resistance-Overcoming Antitumor Activity.Molecular cancer therapeutics · 2026Article
- Illuminating microtubule functions with small molecules: past, present and future of fluorescent tubulin-binding probes.RSC chemical biology · 2026Review
- Combining an anti-HER2 antibody-drug conjugate with an anti-nectin-4 antibody-drug conjugate enhances efficacy in breast cancer and gastric cancer models.Cancer cell international · 2026Article
- Enhancement of recombinant single-cycle viral hemorrhagic septicemia virus replication by modulation of microtubule dynamics using colchicine and paclitaxel.Archives of virology · 2026Article
- Targeting Folate Receptors for the Detection and Selective Treatment of Cancer: Advanced Precision Oncology in Practice.International journal of biological sciences · 2026Review
- Design, Synthesis and Anticancer Activity of 6-Substituted-1-(3,4,5-trimethoxyphenyl)-Molecules (Basel, Switzerland) · 2025Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Recent Advances in Microtubule Targeting Agents for Cancer Therapy.Molecules (Basel, Switzerland) · 2025Review
- Microtubule-Targeting Agents: Advances in Tubulin Binding and Small Molecule Therapy for Gliomas and Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- A review of mirvetuximab soravtansine-gynx in folate receptor alpha-expressing platinum-resistant ovarian cancer.American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists · 2025Review
- Identification of therapeutic targets for chronic kidney disease through Mendelian randomization analysis of druggable genes.Scientific reports · 2025Article
- Identification of a ligand-binding site on tubulin mediating the tubulin-RB3 interaction.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Maytansinoids in cancer therapy: advancements in antibody-drug conjugates and nanotechnology-enhanced drug delivery systems.Discover oncology · 2025Review
- The response regulator CrsR positively regulates ansamitocin P-3 biosynthesis inFrontiers in microbiology · 2025Article
- Computational discovery of potential therapeutic agents against brain-eating amoeba (Naegleria fowleri).PloS one · 2025Article
- Design, synthesis, and bioevaluation of 1Journal of enzyme inhibition and medicinal chemistry · 2024Article
- HURP binding to the vinca domain of β-tubulin accounts for cancer drug resistance.Nature communications · 2024Article
- A phase I safety and efficacy clinical trial of plocabulin and gemcitabine in patients with advanced solid tumors.Investigational new drugs · 2024Article
- Revolutionizing cancer therapy using tetrahedral DNA nanostructures as intelligent drug delivery systems.Nanoscale advances · 2024Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The recent success of antibody-drug conjugates (ADCs) in the treatment of cancer has led to a revived interest in microtubule-destabilizing agents. Here, we determined the high-resolution crystal structure of the complex between tubulin and maytansine, which is part of an ADC that is approved by the US Food and Drug Administration (FDA) for the treatment of advanced breast cancer. We found that the drug binds to a site on β-tubulin that is distinct from the vinca domain and that blocks the formation of longitudinal tubulin interactions in microtubules. We also solved crystal structures of tubulin in complex with both a variant of rhizoxin and the phase 1 drug PM060184. Consistent with biochemical and mutagenesis data, we found that the two compounds bound to the same site as maytansine and that the structures revealed a common pharmacophore for the three ligands. Our results delineate a distinct molecular mechanism of action for the inhibition of microtubule assembly by clinically relevant agents. They further provide a structural basis for the rational design of potent microtubule-destabilizing agents, thus opening opportunities for the development of next-generation ADCs for the treatment of cancer.
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.