ArticleBMC cancer2015
Boronic prodrug of 4-hydroxytamoxifen is more efficacious than tamoxifen with enhanced bioavailability independent of CYP2D6 status.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Developing orally active estrogen receptor degraders by conjugation of boronic tamoxifen and cereblon ligands.European journal of medicinal chemistry · 2026Article
- CreER activation transiently disrupts angiogenesis by reducing proliferation and promoting apoptosis in vascular endothelial cells.Angiogenesis · 2026Article
- An orthogonal TRAP enables intersectional genetic access to activated neurons in the mouse brain.bioRxiv : the preprint server for biology · 2026Article
- Boronate-Based Bioactive Compounds Activated by Peroxynitrite and Hydrogen Peroxide.Redox biochemistry and chemistry · 2024Article
- Advances in the Development of Prodrugs as Selective Modulators of Estrogen Receptors.Journal of the Endocrine Society · 2022Review
- Cre toxicity in mouse models of cardiovascular physiology and disease.Nature cardiovascular research · 2022Article
- The Boron Advantage: The Evolution and Diversification of Boron's Applications in Medicinal Chemistry.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Recent developments in the medicinal chemistry of single boron atom-containing compounds.Acta pharmaceutica Sinica. B · 2021Review
- The Pathogenic Role of Smooth Muscle Cell-Derived Wnt5a in a Murine Model of Lung Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Boronic acid with high oxidative stability and utility in biological contexts.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Development of a bioavailable boron-containing PI-103 Bioisostere, PI-103BE.Bioorganic & medicinal chemistry letters · 2020Article
- Pharmacogenomics of breast cancer: highlighting CYP2D6 and tamoxifen.Journal of cancer research and clinical oncology · 2020Review
- Recent progress in selective estrogen receptor downregulators (SERDs) for the treatment of breast cancer.RSC medicinal chemistry · 2020Review
- Tamoxifen activity against Plasmodium in vitro and in mice.Malaria journal · 2019Article
- Biocompatible Boron-Containing Prodrugs of Belinostat for the Potential Treatment of Solid Tumors.ACS medicinal chemistry letters · 2018Article
- ZB716, a steroidal selective estrogen receptor degrader (SERD), is orally efficacious in blocking tumor growth in mouse xenograft models.Oncotarget · 2018Article
- Metabolism, pharmacokinetics, and bioavailability of ZB716, a Steroidal Selective Estrogen Receptor Downregulator (SERD).Oncotarget · 2017Article
- Rational Design of a Boron-Modified Triphenylethylene (GLL398) as an Oral Selective Estrogen Receptor Downregulator.ACS medicinal chemistry letters · 2017Article
- Fulvestrant-3 Boronic Acid (ZB716): An Orally Bioavailable Selective Estrogen Receptor Downregulator (SERD).Journal of medicinal chemistry · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPoor initial response to tamoxifen due to CYP2D6 polymorphism and adverse side effects are two clinical challenges in tamoxifen therapy. We report the development and preclinical testing of a boronic prodrug to orally deliver 4-OHT at therapeutically effective concentrations but at a fraction of the standard tamoxifen dose.
methodsA mouse xenograft tumor model was used to investigate the efficacy of ZB497 in comparison with tamoxifen. Pharmacokinetic studies were conducted to evaluate the metabolism and bioavailability of the drug in mice. Drug and metabolites distribution in xenograft tumor tissues was determined by high performance liquid chromatography-tandem mass spectrometry.
resultsThe boronic prodrug, ZB497, can not only be efficiently converted to 4-OHT in mice, but also afforded over 30 fold higher plasma concentrations of 4-OHT than in mice given either the same dose of 4-OHT or tamoxifen. Further, ZB497 was more effective than tamoxifen at lowered dosage in inhibiting the growth of xenograft tumors in mice. Consistent with these observations, ZB497 treated mice accumulated over 6 times higher total drug concentrations than tamoxifen treated mice.
conclusionsOur study demonstrates that ZB497 effectively delivers a markedly increased plasma concentration of 4-OHT in mice. The boronic prodrug was shown to have far superior bioavailability of 4-OHT compared to tamoxifen or 4-OHT administration as measured by the area under the plasma concentration time curve (AUC), plasma peak concentrations, and drug accumulation in tumor tissues. Further, ZB497 proves to be a more efficacious hormone therapy than tamoxifen administered at a reduced dose in mice.
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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.