ArticleJournal of medicinal chemistry2018
Heterocyclic-Fused Pyrimidines as Novel Tubulin Polymerization Inhibitors Targeting the Colchicine Binding Site: Structural Basis and Antitumor Efficacy.
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 105 citations in OpenAlex.
- Cytoplasmic lattices store developmentally poised degradative and cytoskeletal complexes in mammalian eggs.Nature structural & molecular biology · 2026Article
- Novel Triazoloquinoxaline-Based Tubulin Polymerization Inhibitor Induces Necroptosis and Significantly Inhibits Metastatic Melanoma Tumor Growth.Journal of medicinal chemistry · 2026Article
- Discovery of a novel potent tubulin inhibitor through virtual screening and target validation for cancer chemotherapy.Cell death discovery · 2025Article
- Design, synthesis, and bioevaluation of 1Journal of enzyme inhibition and medicinal chemistry · 2024Article
- First total synthesis, antitumor evaluation and target identification of mornaphthoate E: A new tubulin inhibitor template acting on PI3K/Akt signaling pathway.Acta pharmaceutica Sinica. B · 2024Article
- Discovery of potent tubulin inhibitors targeting the colchicine binding site via structure-based lead optimization and antitumor evaluation.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Selective isoxazolopyrimidine PAT1 (SLC26A6) inhibitors for therapy of intestinal disorders.RSC medicinal chemistry · 2023Article
- Verubulin (Azixa) Analogues with Increased Saturation: Synthesis, SAR and Encapsulation in Biocompatible Nanocontainers Based on CaPharmaceuticals (Basel, Switzerland) · 2023Article
- Fused Imidazopyrazine-Based Tubulin Polymerization Inhibitors Inhibit Neuroblastoma Cell Function.ACS medicinal chemistry letters · 2023Article
- Exploring Pyrrolo-Fused Heterocycles as Promising Anticancer Agents: An Integrated Synthetic, Biological, and Computational Approach.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Design, Synthesis, and Biological Evaluation of Pyrimidine Dihydroquinoxalinone Derivatives as Tubulin Colchicine Site-Binding Agents That Displayed Potent Anticancer Activity Both In Vitro and In Vivo.ACS pharmacology & translational science · 2023Article
- SB226, an inhibitor of tubulin polymerization, inhibits paclitaxel-resistant melanoma growth and spontaneous metastasis.Cancer letters · 2023Article
- Cancer targeted drug delivery using active low-density lipoprotein nanoparticles encapsulated pyrimidines heterocyclic anticancer agents as microtubule inhibitors.Drug delivery · 2022Article
- Colchicine-Binding Site Agent CH-2-77 as a Potent Tubulin Inhibitor Suppressing Triple-Negative Breast Cancer.Molecular cancer therapeutics · 2022Article
- Molecular interactions at the colchicine binding site in tubulin: An X-ray crystallography perspective.Drug discovery today · 2022Review
- Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-Molecules (Basel, Switzerland) · 2022Article
- X-ray Crystallography-Guided Design, Antitumor Efficacy, and QSAR Analysis of Metabolically Stable Cyclopenta-Pyrimidinyl Dihydroquinoxalinone as a Potent Tubulin Polymerization Inhibitor.Journal of medicinal chemistry · 2021Article
- Design, Synthesis, and Biological Evaluation of Stable Colchicine-Binding Site Tubulin Inhibitors 6-Aryl-2-benzoyl-pyridines as Potential Anticancer Agents.Journal of medicinal chemistry · 2021Article
- Discovery of Novel DiarylamideMolecules (Basel, Switzerland) · 2021Article
- Novel pyrazolo[4,3-d]pyrimidine microtubule targeting agents (MTAs): Synthesis, structure-activity relationship, in vitro and in vivo evaluation as antitumor agents.Bioorganic & medicinal chemistry letters · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
We report the design, synthesis, and biological evaluation of heterocyclic-fused pyrimidines as tubulin polymerization inhibitors targeting the colchicine binding site with significantly improved therapeutic index. Additionally, for the first time, we report high-resolution X-ray crystal structures for the best compounds in this scaffold, 4a, 4b, 6a, and 8b. These structures not only confirm their direct binding to the colchicine site in tubulin and reveal their detailed molecular interactions but also contrast the previously published proposed binding mode. Compounds 4a and 6a significantly inhibited tumor growth in an A375 melanoma xenograft model and were accompanied by elevated levels of apoptosis and disruption of tumor vasculature. Finally, we demonstrated that compound 4a significantly overcame clinically relevant multidrug resistance in a paclitaxel resistant PC-3/TxR prostate cancer xenograft model. Collectively, these studies provide preclinical and structural proof of concept to support the continued development of this scaffold as a new generation of tubulin inhibitors.
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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.