ArticleBioorganic & medicinal chemistry2018
α-Methylation enhances the potency of isoprenoid triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.
Article in Bioorganic & medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Incorporation of an alpha-hydroxy substituent modulates activity of triazole bisphosphonate-based geranylgeranyl diphosphate synthase inhibitors.Bioorganic & medicinal chemistry · 2026Article
- The effects of geranylgeranyl diphosphate synthase inhibitor treatment on osteoblast biology and application in a conditioned media model of myeloma bone disease.Bone reports · 2025Article
- Impact of fixed phosphorus position on activity of triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.Bioorganic & medicinal chemistry · 2025Article
- Structure-activity relationship of isoprenoid triazole bisphosphonate-based geranylgeranyl diphosphate synthase inhibitors: Effects on pharmacokinetics, biodistribution, and hepatic transporters.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Geranylgeranyl diphosphate synthase inhibition impairs osteoclast differentiation, morphology, and resorptive activity.JBMR plus · 2025Article
- α-Amino bisphosphonate triazoles serve as GGDPS inhibitors.Bioorganic & medicinal chemistry letters · 2024Article
- Structural Insight into Geranylgeranyl Diphosphate Synthase (GGDPS) for Cancer Therapy.Molecular cancer therapeutics · 2024Review
- Evaluation of geranylgeranyl diphosphate synthase inhibition as a novel strategy for the treatment of osteosarcoma and Ewing sarcoma.Drug development research · 2023Article
- Geranylgeranyl diphosphate synthase: Role in human health, disease and potential therapeutic target.Clinical and translational medicine · 2023Review
- Targeting the Isoprenoid Biosynthetic Pathway in Multiple Myeloma.International journal of molecular sciences · 2022Review
- Conjugate reduction of vinyl bisphosphonates.Tetrahedron letters · 2022Article
- Prodrugs of pyrophosphates and bisphosphonates: disguising phosphorus oxyanions.RSC medicinal chemistry · 2022Review
- Article
- Geranylgeranyl diphosphate synthase inhibitor and proteasome inhibitor combination therapy in multiple myeloma.Experimental hematology & oncology · 2022Article
- Impact of α-modifications on the activity of triazole bisphosphonates as geranylgeranyl diphosphate synthase inhibitors.Bioorganic & medicinal chemistry · 2021Article
- Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.Journal of medicinal chemistry · 2021Review
- Amides as bioisosteres of triazole-based geranylgeranyl diphosphate synthase inhibitors.Bioorganic & medicinal chemistry · 2020Article
- Phosphonate and Bisphosphonate Inhibitors of Farnesyl Pyrophosphate Synthases: A Structure-Guided Perspective.Frontiers in chemistry · 2020Review
- Targeting prenylation inhibition through the mevalonate pathway.RSC medicinal chemistry · 2020Review
- Novel benzimidazole phosphonates as potential inhibitors of protein prenylation.Bioorganic & medicinal chemistry letters · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Disruption of protein geranylgeranylation via inhibition of geranylgeranyl diphosphate synthase (GGDPS) represents a novel therapeutic strategy for a variety of malignancies, especially those characterized by excessive protein secretion such as multiple myeloma. Our work has demonstrated that some isoprenoid triazole bisphosphonates are potent and selective inhibitors of GGDPS. Here we present the synthesis and biological evaluation of a new series of isoprenoid triazoles modified by incorporation of a methyl group at the α-carbon. These studies reveal that incorporation of an α-methyl substituent enhances the potency of these compounds as GGDPS inhibitors, and, in the case of the homogeranyl/homoneryl series, abrogates the effects of olefin stereochemistry on inhibitory activity. The incorporation of the methyl group allowed preparation of a POM-prodrug, which displayed a 10-fold increase in cellular activity compared to the corresponding salt. These studies form the basis for future preclinical studies investigating the anti-myeloma activity of these novel α-methyl triazole bisphosphonates.
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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 Socratic graph.