ArticleChemMedChem2016
Targeting Cancer Cells with a Bisphosphonate Prodrug.
Article in ChemMedChem, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 41 citations in OpenAlex.
- Anti-tumor efficacy and Vδ2 T-cell activation via EGFR antibody-drug conjugates featuring novel aminobisphosphonates.Scientific reports · 2025Article
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- Ultrasound-assisted synthesis of new bisphosphonate-betulin conjugates and preliminary evaluation of their cytotoxic activity.RSC advances · 2025Article
- Human Vγ9Vδ2 T cells exhibit antifungal activity againstMicrobiology spectrum · 2024Article
- Thiazole, Isatin and Phthalimide Derivatives TestedCurrent medicinal chemistry · 2024Review
- CAR-Modified Vγ9Vδ2 T Cells Propagated Using a Novel Bisphosphonate Prodrug for Allogeneic Adoptive Immunotherapy.International journal of molecular sciences · 2023Article
- Article
- EBV latent membrane protein 1 augments γδ T cell cytotoxicity against nasopharyngeal carcinoma by induction of butyrophilin molecules.Theranostics · 2023Article
- Two Distinct Mechanisms Underlying γδ T Cell-Mediated Regulation of Collagen Type I in Lung Fibroblasts.Cells · 2022Article
- Prodrugs of pyrophosphates and bisphosphonates: disguising phosphorus oxyanions.RSC medicinal chemistry · 2022Review
- Bisphosphonates Targeting Ion Channels and Musculoskeletal Effects.Frontiers in pharmacology · 2022Review
- Hydroxy- and Amino-Phosphonates and -Bisphosphonates: Synthetic Methods and Their Biological Applications.Frontiers in chemistry · 2022Review
- Article
- The role of small molecules in cell and gene therapy.RSC medicinal chemistry · 2021Review
- New Progress in Improving the Delivery Methods of Bisphosphonates in the Treatment of Bone Tumors.Drug design, development and therapy · 2021Review
- Structure-Activity Relationships of Butyrophilin 3 Ligands.ChemMedChem · 2020Review
- Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells.Heliyon · 2020Article
- Liposome-Encapsulated Zoledronate Favors Tumor Vascular Normalization and Enhances Anticancer Efficacy of Cisplatin.AAPS PharmSciTech · 2020Article
- Phosphonate and Bisphosphonate Inhibitors of Farnesyl Pyrophosphate Synthases: A Structure-Guided Perspective.Frontiers in chemistry · 2020Review
- Comparison of a Novel Bisphosphonate Prodrug and Zoledronic Acid in the Induction of Cytotoxicity in Human Vγ2Vδ2 T Cells.Frontiers in immunology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Nitrogen-containing bisphosphonates have antitumor activity in certain breast cancer and myeloma patients. However, these drugs have limited oral absorption, tumor cell entry and activity, and cause bone side effects. The potencies of phosphorylated antiviral drugs have been increased by administering them as prodrugs, in which the negative charges on the phosphate moieties are masked to make them lipophilic. We synthesized heterocyclic bisphosphonate (BP) prodrugs in which the phosphonate moieties are derivatized with pivaloyloxymethyl (pivoxil) groups and that lack the hydroxy "bone hook" on the geminal carbon. When the lipophilic BP prodrugs enter tumor cells, they are converted into their active forms by intracellular esterases. The most active BP prodrug, tetrakispivaloyloxymethyl 2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate (7), was found to potently inhibit the in vitro growth of a variety of tumor cell lines, especially hematopoietic cells, at nanomolar concentrations. Consistent with this fact, compound 7 inhibited the prenylation of the RAP1A small GTPase signaling protein at concentrations as low as 1-10 nm. In preclinical studies, 7 slowed the growth of human bladder cancer cells in an immunodeficient mouse model. Thus, 7 is significantly more active than zoledronic acid, the most active FDA-approved BP, and a potential anticancer therapeutic.
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.