ArticleJournal of medicinal chemistry2018
Fluorine-Substituted Pyrrolo[2,3- d]Pyrimidine Analogues with Tumor Targeting via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis.
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 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- ATIC facilitates the malignant progression of bladder cancer by modulating AMPK-mTOR-S6K1 axis under folate reprogramming.Journal of translational medicine · 2026Article
- Mitochondrial and Cytosolic One-Carbon Metabolism Is a Targetable Metabolic Vulnerability in Cisplatin-Resistant Ovarian Cancer.Molecular cancer therapeutics · 2024Article
- Discovery of Tumor-Targeted 6-Methyl Substituted Pemetrexed and Related Antifolates with Selective Loss of RFC Transport.ACS medicinal chemistry letters · 2023Article
- Structure-Based Design of Transport-Specific Multitargeted One-Carbon Metabolism Inhibitors in Cytosol and Mitochondria.Journal of medicinal chemistry · 2023Article
- Multitargeted 6-Substituted Thieno[2,3-ACS pharmacology & translational science · 2023Article
- Biology and therapeutic applications of the proton-coupled folate transporter.Expert opinion on drug metabolism & toxicology · 2022Article
- Targeted therapy of pyrrolo[2,3-d]pyrimidine antifolates in a syngeneic mouse model of high grade serous ovarian cancer and the impact on the tumor microenvironment.Scientific reports · 2022Article
- Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer.Cancers · 2021Review
- Discovery of 6-substituted thieno[2,3-d]pyrimidine analogs as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis in folate receptor expressing human tumors.Bioorganic & medicinal chemistry · 2021Article
- Folate transporter dynamics and therapy with classic and tumor-targeted antifolates.Scientific reports · 2021Article
- Design, synthesis and biological evaluation of novel pyrrolo[2,3-d]pyrimidine as tumor-targeting agents with selectivity for tumor uptake by high affinity folate receptors over the reduced folate carrier.Bioorganic & medicinal chemistry · 2020Article
- Cellular Pharmacodynamics of a Novel Pyrrolo[3,2-Molecular pharmacology · 2020Article
- Novel Pyrrolo[3,2-Molecular cancer therapeutics · 2019Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Novel fluorinated 2-amino-4-oxo-6-substituted pyrrolo[2,3- d]pyrimidine analogues 7-12 were synthesized and tested for selective cellular uptake by folate receptors (FRs) α and β or the proton-coupled folate transporter (PCFT) and for antitumor efficacy. Compounds 8, 9, 11, and 12 showed increased in vitro antiproliferative activities (∼11-fold) over the nonfluorinated analogues 2, 3, 5, and 6 toward engineered Chinese hamster ovary and HeLa cells expressing FRs or PCFT. Compounds 8, 9, 11, and 12 also inhibited proliferation of IGROV1 and A2780 epithelial ovarian cancer cells; in IGROV1 cells with knockdown of FRα, 9, 11, and 12 showed sustained inhibition associated with uptake by PCFT. All compounds inhibited glycinamide ribonucleotide formyltransferase, a key enzyme in the de novo purine biosynthesis pathway. Molecular modeling studies validated in vitro cell-based results. NMR evidence supports the presence of an intramolecular fluorine-hydrogen bond. Potent in vivo efficacy of 11 was established with IGROV1 xenografts in severe compromised immunodeficient mice.
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Registered trials
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